研究者データベース

菅原 満(スガワラ ミツル)
薬学研究院 医療薬学部門 医療薬学分野
教授

基本情報

所属

  • 薬学研究院 医療薬学部門 医療薬学分野

職名

  • 教授

学位

  • 博士(薬学)(北海道大学)

J-Global ID

研究キーワード

  • 生物薬剤学   薬物動態学   

研究分野

  • ライフサイエンス / 医療薬学

職歴

  • 2009年04月 - 現在 北海道大学 大学院薬学研究院 教授
  • 2007年04月 - 2009年03月 北海道大学病院 薬剤部 薬剤部副部長・准教授
  • 2000年11月 - 2007年03月 北海道大学病院 薬剤部 薬剤部副部長・助教授
  • 1998年11月 - 2000年10月 ジョージア医科大学 生化学・分子生物学研究室 博士研究員
  • 1989年04月 - 1998年10月 北海道大学医学部附属病院 薬剤師

学歴

  • 1987年04月 - 1989年03月   北海道大学   薬学研究科薬学専攻   修士課程
  •         - 1987年03月   北海道大学   薬学部   薬学科

所属学協会

  • 日本薬剤学会   日本TDM学会   日本臨床薬理学会   日本医療薬学会   日本薬物動態学会   日本薬学会   

研究活動情報

論文

  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Tomohiro Oshino, Mitsuru Sugawara
    Scientific reports 12 1 12587 - 12587 2022年07月22日 [査読有り][通常論文]
     
    Oral mucositis (OM) is one of the most common complications associated with chemotherapy. Here, we evaluated whether systemic dexamethasone (DEX) dosage in prophylactic antiemetics affected the incidence of OM in anthracycline-containing regimens. Patients receiving anthracycline-containing regimens for breast cancer were divided into high- and low-DEX dose groups and retrospectively evaluated. The incidence of all-grade OM in the first cycle in the high- and low-dose groups was 27.3% and 53.5%, respectively, and was significantly lowered by increasing the DEX dose (P < 0.01); thus, the study met its primary endpoint. The result in all treatment cycles was also significant (P = 0.02). In contrast, the incidence of dysgeusia was similar between the high- and low-dose groups in the first and all cycles (13.6% and 16.3% in the first cycle [P = 0.79] and 27.3% and 34.9% in all cycles [P = 0.42], respectively). Multivariate analysis revealed that low DEX dosage was an independent risk factor for all-grade OM development. In conclusion, our study suggests that DEX attenuates OM in anthracycline-containing regimens for breast cancer treatment in a dose-dependent manner. Further evaluation of OM prophylaxis, including DEX administration, is required for better control.
  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Mitsuru Sugawara
    Anticancer research 42 7 3753 - 3758 2022年07月 [査読有り][通常論文]
     
    BACKGROUND/AIM: The incidence of acute nausea in patients treated with anthracycline-containing regimens for breast cancer, was significantly increased by dose reduction of prophylactic antiemetic dexamethasone on day 1, whilst reducing it on days 2-4 did not affect delayed nausea. We also found that patients <55 years old were at higher risk of developing nausea. In this retrospective study, we evaluated the influence of dexamethasone dosage on gastrointestinal symptoms in patients <55 years old. PATIENTS AND METHODS: Patients (20-54 years old) who had received anthracycline-containing regimens for breast cancer were divided into reduced dose (6.6 mg dexamethasone on day 1, and 4 mg on days 2-4) and control (9.9 mg and 8 mg, respectively) groups and retrospectively evaluated. The incidence and severity of nausea, vomiting and anorexia were compared. Risk factors associated with nausea were also assessed. RESULTS: The incidence of acute nausea was significantly higher in the reduced dosage group than in the control group (75.0% and 45.2%, respectively; p=0.02). In contrast, the rate of delayed nausea was not different (p=0.41); the incidence of vomiting and anorexia, and the severity of nausea and anorexia were also not statistically different. Multivariate logistic analysis suggested that patients with no-to-low alcohol consumption and those administered 6.6 mg dexamethasone on day 1 were at a higher risk of acute nausea. CONCLUSION: Our study suggests that dexamethasone dose reduction on day 1 in patients treated with anthracycline-containing regimens is not suitable for acute nausea management, and that the dosage can be reduced to at least 4 mg on days 2-4, even in patients under 55 years of age.
  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Mitsuru Sugawara
    Anticancer research 42 7 3693 - 3700 2022年07月 [査読有り][通常論文]
     
    BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for the treatment of metastatic breast cancer and advanced or metastatic soft-tissue sarcomas. However, severe adverse effects (SAEs) occur in 30-40% of the patients, and significantly reduce the patients' quality of life and disturb the recommended treatment schedules. Neutropenia is the main cause of treatment suspension, delay, and/or dose reductions, also leading to relative dose intensity reduction. This study aimed to examine the risk factors for SAE occurrence after eribulin treatment. PATIENTS AND METHODS: Eighty patients with metastatic breast cancer or advanced or metastatic soft tissue sarcoma who received eribulin were retrospectively evaluated. Risk factors for SAE occurrence in the first cycle were primarily assessed. In addition, factors associated with SAE occurrence during all treatment cycles were evaluated. RESULTS: SAEs in the first cycle occurred in 45% of patients. The primary SAE was neutropenia (91.7%). The incidence of SAEs during all treatment cycles was 61.3%. Multivariate analyses suggested that lower baseline neutrophil and hemoglobin levels were risk factors for SAE occurrence and severe neutropenia incidence in the first cycle. An independent factor associated with SAE occurrence during all cycles was age ≥65 years and a tendency was confirmed for baseline anemia. CONCLUSION: Baseline neutropenia and anemia were risk factors for SAE occurrence during the first eribulin treatment cycle. Age ≥65 years was also associated with SAE occurrence during all treatment cycles. Patients with these risk factors should be carefully monitored for assessment and prophylaxis.
  • Yoshitaka Saito, Yoh Takekuma, Tomohiro Oshino, Mitsuru Sugawara
    Case Reports in Oncology 606 - 610 2022年06月10日 [査読有り][通常論文]
     
    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most severe complications associated with chemotherapy for breast cancer. We encountered a case in which mirogabalin initially ameliorated, and additional duloxetine further attenuated eribulin-induced CIPN. Herein, we report its management. A 53-year-old woman received eribulin treatment as third-line chemotherapy for recurrent breast cancer. She experienced grade 2 CIPN with adjuvant docetaxel and cyclophosphamide treatment (worst numeric rating scale (NRS) 6/10 for numbness and 6/10 for pain) and had baseline grade 1 symptoms only in the hands (NRS 1/10 for each). CIPN in the hands and feet worsened to NRS 3/10 on day 1 of cycle 4. Mirogabalin (5 mg twice daily) was initiated, resulting in stable symptoms for approximately 6 weeks with grade 1 somnolence and heaviness of the head. The dosage was increased with careful attention to adverse effects to 22.5 mg per day, and the NRS was reduced from 5/10 to 3/10 for numbness and from 8/10 to 5/10 for pain. We administered duloxetine 20 mg with domperidone (10 mg three times a day) for further pain attenuation on day 1 of cycle 15, decreasing the NRS to 1/10 for numbness and 3/10 for pain. Duloxetine was increased due to CIPN degradation (NRS 3/10 and 5/10), resulting in a significant pain attenuation to 1/10. As the CIPN-attenuating mechanisms of mirogabalin and duloxetine are different, we consider that the additive and synergetic effects of this combination affected the results. Combination therapy with these drugs may be a promising strategy.
  • Keisuke Kagami, Nobuhisa Ishiguro, Sumio Iwasaki, Takayuki Usami, Tatsuya Fukumoto, Kasumi Hayasaka, Reiko Oyamada, Tsubasa Watanabe, Sho Nakakubo, Yusuke Niinuma, Takashi Hagino, Yoshifumi Abe, Ikuya Fujimoto, Hideki Maekawa, Ryo Fujibayashi, Satoshi Fuke, Kuniko Asahi, Shuichi Ota, Tatsuya Nagakura, Toshinari Okubo, Hideomi Asanuma, Toshihiro Ito, Sho Okano, Erika Komatsu, Kota Sasaki, Kei Hashimoto, Kazutoshi Washiya, Yumiko Kato, Katsunori Kusumi, Yasufumi Asai, Yuichi Saito, Yoshiyuki Sakai, Minoru Sakurada, Yuji Sakimoto, Yukari Ichikawa, Takahiro Kinebuchi, Dai Kondo, Syuhei Kanno, Minoru Kobayashi, Kagami Hirabayashi, Shinako Saitou, Katsuhiko Saito, Yuuki Ebina, Yuusuke Koshizaki, Makoto Chiba, Atsushi Yasuda, Toshiya Sato, Atsuo Togashi, Takashi Abe, Takahiro Fujita, Kengo Umehara, Masaru Amishima, Nobuo Murakami, Tetsuya Yagi, Shuhei Fujimoto, Taichi Tajima, Mitsuru Sugawara, Yoh Takekuma
    American journal of infection control 2022年06月04日 [査読有り][通常論文]
     
    BACKGROUND: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan. METHODS: Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro. RESULTS: The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = 0.015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = 0.023), ρ = 0.76 (P < 0.001), and ρ = 0.502 (P = 0.029), respectively]. CONCLUSION: This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.
  • Yoshitaka Saito, Yoh Takekuma, Masaki Kobayashi, Naofumi Shinagawa, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Mitsuru Sugawara
    Anticancer research 42 6 3185 - 3193 2022年06月 [査読有り][通常論文]
     
    BACKGROUND/AIM: Short hydration is a method to change partial intravenous hydration to oral to administer cisplatin (CDDP); however, the most suitable form of oral hydration is unknown. This study aimed to determine whether oral rehydration solution (ORS) affects CDDP-induced nephrotoxicity (CIN) and electrolyte imbalance. PATIENTS AND METHODS: Lung cancer patients (n=200) who had received CDDP-including regimens (CDDP dosage ≥75 mg/m2) were retrospectively evaluated. We used logistic analysis to evaluate whether ORS intake could be a preventive factor for CIN (≥grade 2 serum creatinine elevation). Moreover, incidence of CIN and electrolyte imbalance and the variation in serum creatinine and electrolyte levels were compared between ORS and non-ORS (control) patients. RESULTS: CIN occurred in 9.8% of ORS patients, and 7.5% of non-ORS patients (p=0.79). The variation in serum creatinine level was also similar in both groups. Multivariate analysis suggested that ORS intake does not affect CIN, although CIN was associated with the coadministration of non-steroidal anti-inflammatory drugs and the presence of diabetes mellitus. The variations in serum electrolyte levels did not differ, and incidence of hyponatremia, hypokalemia, and hypochloremia was also similar between the groups. Moreover, patients in ORS group experienced significantly more anorexia compared to controls, and approximately 40% of the patients were unable to continue ORS intake. CONCLUSION: ORS intake in CDDP short hydration regimens does not affect CIN and CDDP-induced electrolyte imbalance; however, its intake is associated with the incidence of anorexia suggesting that ORS should not be used for oral hydration.
  • 今井 俊吾, 柏木 仁, 佐藤 夕紀, 武隈 洋, 菅原 満
    医薬品情報学 24 1 1 - 10 (一社)日本医薬品情報学会 2022年05月 [査読有り][通常論文]
  • Soyoko Kaburaki, Eri Yoshimura, Yasushi Miyamoto, Shungo Imai, Hitoshi Kashiwagi, Hidefumi Ueno, Mitsuru Sugawara, Yoh Takekuma
    Geriatrics & gerontology international 22 5 449 - 454 2022年05月 [査読有り][通常論文]
     
    AIM: Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. METHODS: Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. RESULTS: Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m2 ) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI ≥36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. CONCLUSIONS: Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients. Geriatr Gerontol Int 2022; 22: 449-454.
  • 武隈 洋, 今井 俊吾, 菅原 満
    薬学雑誌 142 4 331 - 336 (公社)日本薬学会 2022年04月 [査読有り][通常論文]
  • Akira Yamagami, Katsuya Narumi, Yoshitaka Saito, Ayako Furugen, Shungo Imai, Yoshimasa Kitagawa, Yoichi Ohiro, Ryo Takagi, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi
    Journal of clinical pharmacy and therapeutics 2022年03月07日 [査読有り][通常論文]
     
    WHAT IS KNOWN AND OBJECTIVE: Third-generation oral cephalosporins, especially cefcapene-pivoxil (CFPN-PI), have been used frequently in the Japanese dental field. In December 2014 and April 2016, the newly published clinical guidelines recommended the use of amoxicillin (AMPC). Thus, it is important to evaluate the impact of these guidelines on the prescription profiles of prophylactic antibiotics, clinical outcomes and cost-effectiveness of antibiotics. METHODS: We conducted a retrospective study to analyse an interrupted time series analysis from April 2013 to March 2020 at the Department of Dentistry of Hokkaido University Hospital. A segmented regression model was used to estimate the changes in the incidence of infectious complications following tooth extraction. Prescribed antibiotic data were evaluated via days of therapy (DOT). Antibiotic costs were calculated in terms of the Japanese yen (JPY). RESULTS AND DISCUSSION: We identified 17,825 eligible patients. The incidence rates of infectious complications (SSI + dry socket) and SSI after tooth extraction were 3.2% and 2.2%, respectively, during the entire period. The extraction of impacted third molars corresponded to 5.0% and 3.4%, respectively. However, their incidence rates were not significantly different during this period. The use of prophylactic antibiotics and antibiotic cost showed consistent trends following the implementation of guidelines. The mean DOT of CFPN-PI decreased (ranging from 4893.6 DOTs/1000 patients [March 2013 to November 2014] to 3856.4 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3856.4 DOTs/1000 patients [December 2014 to March 2016] to 2293.9 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). In contrast, the mean DOT of AMPC was found to be increased (ranging from 1379.7 DOTs/1000 patients [March 2013 to November 2014] to 3236.3 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3236.3 DOTs/1000 patients [December 2014 to March 2016] to 4597.8 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). The mean monthly cost was decreased (ranging from 905.3 JPY [March 2013 to November 2014] to 788.7 JPY [December 2014 to March 2016]; p = 0.003, and from 788.7 JPY [December 2014 to March 2016] to 614.0 JPY [April 2016 to March 2020]; p < 0.001). WHAT IS NEW AND CONCLUSION: After December 2014, prophylactic antibiotics were switched from CFPN-PI to AMPC, and the incidence rate of infectious complications was not significantly different over time. However, changing antibiotics is useful from a cost-effectiveness perspective.
  • Shungo Imai, Shota Kadomura, Takayuki Miyai, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Yoh Takekuma
    British journal of clinical pharmacology 88 7 3241 - 3255 2022年02月01日 [査読有り]
     
    AIMS: Several factors related to vancomycin-induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high-risk combinations that influence VIN. METHODS: We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 1.5-fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method. RESULTS: Of the 7,306 patients that were enrolled, VIN occurred in 14.2% of them (1,035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio; 0.701, 95% confidence interval; 0.512-0.959), ward pharmacy service (0.741, 0.638-0.861), duration of VCM <7 days (0.748, 0.623-0.899) and trough concentrations 10-15 mg/L (0.668, 0.556-0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin-tazobactam use (2.056, 1.754-2.409) and piperacillin use (2.868, 1.298-6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin-tazobactam use was associated with the highest risk. CONCLUSIONS: We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin-tazobactam but also piperacillin may increase the risk.
  • Yoshitaka Saito, Yoh Takekuma, Naofumi Shinagawa, Mitsuru Sugawara
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 5 4081 - 4088 2022年01月23日 [査読有り][通常論文]
     
    PURPOSE: Carboplatin (CBDCA) + nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the most effective chemotherapeutic regimens for advanced non-small cell lung cancer (NSCLC) treatment. However, neutropenia and neuropathy are well-known dose-limiting toxicities associated with this regimen, frequently resulting in treatment suspension and dose reduction. In the present study, we aimed to identify risk factors associated with CBDCA + nab-PTX treatment suspension. METHODS: Patients with NSCLC who received CBDCA + nab-PTX ± atezolizumab or pembrolizumab regimens were retrospectively evaluated. The risk factor(s) for treatment suspension and primary causes underlying suspension during the first course were assessed; the relative dose intensity (RDI) was compared between patients with and without identified factors. RESULTS: The frequency of treatment suspension was determined as 55%. The causes for suspension were neutropenia (65.2%), infection (24.2%), thrombocytopenia (6.1%), and other conditions. The calculated RDI was 98.5% for CBDCA and 79.3% for nab-PTX. Based on univariate and multivariate analyses, grade 1 or higher liver dysfunction was identified as a risk factor for treatment suspension. We determined primary causes for treatment suspension as neutropenia and/or infection, as they are closely related. Next, we evaluated associated factors and determined age ≥65 years and performance status (PS) 2 as potential factors, in addition to liver dysfunction. CONCLUSION: We observed that liver dysfunction at baseline is a risk factor for treatment suspension. In addition, age ≥65 years and PS 2 can result in treatment suspension owing to neutropenia and/or infection during CBDCA + nab-PTX treatment.
  • Takayuki Miyai, Shungo Imai, Eri Yoshimura, Hitoshi Kashiwagi, Yuki Sato, Hidefumi Ueno, Yoh Takekuma, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 45 9 1332 - 1339 2022年 [査読有り][通常論文]
     
    In therapeutic drug monitoring of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to clinical efficacy and toxicity. Determining the maintenance for patient is necessary since VCM concentrations are affected by factors such as renal function. We constructed a machine learning-based model to estimate the maintenance dose to target an AUC of 400-600 mg⋅h/L in each combination of patient's factors. This retrospective observational study was conducted at two hospitals. Patients who received VCM intravenously with measured trough and another point (e.g., peak) concentrations within the November 2011 to March 2019 period were enrolled. We extracted the factors that affect VCM concentration and constructed a decision tree model using a classification and regression tree algorithm. Of the 1380 patients, 822 were included. Training data were split up to four times and included 24 subgroups. The average corrected VCM daily doses ranged 17.6-59.4 mg/kg. Estimated glomerular filtration rate, age, and body mass index were selected as predictive variables that affected the recommended daily dose. In the validation data, our model had slightly higher proportions of AUC of 400-600 mg⋅h/L than other nomograms. However, our model was based only on limited patients. Thus, further clinical studies are needed to develop a general-purpose model in the future. We successfully constructed a model that recommends VCM maintenance daily doses with AUC of 400-600 mg⋅h/L for each combination of independent variables. Our model has the potential for application as a simple decision-making tool for medical staff.
  • Seika Kitamura, Ayako Nishimura, Yoh Takekuma, Yoshitaka Saito, Takeshi Umazume, Mitsuru Sugawara
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 142 9 1031 - 1035 2022年 [査読有り][通常論文]
     
    Lacosamide is a novel antiepileptic drug. Although many antiepileptic drugs reportedly pose a risk to fetuses, patients with epilepsy are advised to continue their medications during pregnancy. There have been few reports on lacosamide use during pregnancy, and its effects on the fetus remain unclear. Here, we report a case of lacosamide use during pregnancy. The 33-year-old patient was treated with oral lacosamide (400 mg/d) for symptomatic partial epilepsy. She was concomitantly treated with folic acid (5 mg/d) beginning 4 days before her last menstrual cycle. She was also concomitantly treated with oral perampanel (2 mg/d) at 5-7 weeks' gestation for seizure control but discontinued perampanel after the pregnancy was discovered. She progressed through her pregnancy with only mild seizures. Fetal growth was normal and ultrasonography revealed no external malformations. The patient had an elective cesarean section at 37 weeks and 2 days owing to a previous post-cesarean pregnancy. Her baby boy weighed 3025 g; his Apgar score was 8 and 9, 1 and 5 min, respectively, and his umbilical artery blood pH was 7.348. He had no congenital anomalies and no neonatal drug withdrawal symptoms. This suggests that lacosamide may have a low risk of teratogenicity and fetal toxicity. Thus, this case is valuable for clinicians who are considering the administration of antiepileptic drugs during pregnancy. In the future, more reports on the use of lacosamide during pregnancy should be collected.
  • Shintaro Kato, Yoshitaka Saito, Hiroko Onoda, Masayoshi Kumai, Shungo Imai, Kenkichi Tsuruga, Yoh Takekuma, Mitsuru Sugawara
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 142 7 755 - 760 2022年 [査読有り][通常論文]
     
    Naldemedine (Nal) is widely used as a therapeutic drug against opioid-induced constipation. However, patients in phase III trials are limited to those with good performance status (PS). Cancer patients may have inferior PS owing to progression of symptoms and adverse events from chemotherapy. Therefore, it is important to survey the efficacy of Nal in patients with poor PS. This study aimed to evaluate Nal efficacy in patients with poor PS. We retrospectively investigated patients from July 2017 to June 2019 and compared Nal efficacy between patients with good and poor PS. The efficacy of Nal was evaluated using changes in the number of spontaneous bowel movements 7 days before and after the introduction of Nal with reference to previous reports. Multivariate analysis was performed to reveal whether poor PS affects Nal efficacy. In total, 141 patients at the Hokkaido University Hospital were analyzed. The effective rate of Nal from day 1 to day 7 of administration was 71.7% and 71.4% in the patients with good and poor PS, respectively, that from day 1 to day 2 of administration was 61.1% and 57.1%, respectively, and that from day 3 to day 7 of administration was 60.2% and 71.4%, respectively, suggesting an absence of significant differences. Furthermore, results of multivariate analysis showed that "best supportive care" and "body weight (55 kg and above)" reduced Nal efficacy. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Annals of Clinical Epidemiology 4 1 6 - 10 2022年 [査読有り][通常論文]
  • Yoh Takekuma, Shungo Imai, Mitsuru Sugawara
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 142 4 331 - 336 2022年 [査読有り][通常論文]
     
    The JMDC Claims Database® contains completely anonymized receipt information on the insured members of health insurance associations. The number of registered users is approximately 9.6 million (6% of the population) as of May 2020. In this database, it is possible to track even outpatient treatment, even if the patient changes the medical facility, as long as the insurer of the subscriber's health insurance does not change, so that long-term medical treatment could be targeted as a research theme. However, as the data do not contain medical record information, it is not possible to obtain laboratory values, although it is possible to know whether clinical tests have been performed. For pharmaceutics-related research, the most suitable use of the receipt database like JMDC Claims Database® seems to be the investigation of actual prescriptions. However, the research topics that pharmacists are interested in are probably comparisons of drug effects, drug-drug interactions, or causal analysis of drugs and side effects. However, laboratory data for evaluating drug efficacy is not available in the receipt database, and the accuracy of the disease name in the database becomes problematic when using the disease name as information indicating the occurrence of side effects. In this review, we introduce our studies performed by using JMDC Claims Database® and how to manage the above-described problems. We hope that this study will be helpful to those who are going to engage in research using medical big data.
  • Yuki Sato, Yoh Takekuma, Takayuki Daisho, Hitoshi Kashiwagi, Shungo Imai, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 45 4 421 - 428 2022年 [査読有り][通常論文]
     
    It is important to select appropriate antibiotics for infection control. Linezolid and tedizolid are newly developed and synthesized oxazolidinone antibacterial agents. It has been pointed out that there is a relationship between a high plasma concentration of the target drug and incidence of adverse effects, although it has been reported that neither linezolid nor tedizolid requires dose adjustment according to renal function. Due to the high incidence of adverse effects, both are often switched. Precise plasma concentration control by therapeutic drug monitoring (TDM) is desirable for reducing the adverse effects of both drugs and obtaining a better therapeutic effect. In this study, we aimed to establish a method for simultaneous quantification of linezolid and tedizolid in human plasma using LC coupled with tandem mass spectrometry. Sample preparation was performed by a simple operation with acetonitrile. Linezolid and tedizolid were separated by an octadecylsilyl column using a gradient elution of acetonitrile in aqueous 0.1% formic acid solution and were detected in the positive ion electrospray mode with multiple reaction monitoring. Quantification of linezolid and tedizolid ranged from 0.5 to 50 and 0.5 to 20 µg/mL, respectively. The intra-day and inter-day precision and accuracy of data were assessed and found to be acceptable. The developed method was successfully applied to measurement of the concentrations of linezolid and tedizolid. This simple method, which can simultaneously quantify both drug concentrations for daily TDM, could contribute to safer treatment of patients.
  • Kazuki Uchiyama, Yoshitaka Saito, Tatsuhiko Sakamoto, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Anticancer research 42 1 343 - 348 2022年01月 [査読有り][通常論文]
     
    BACKGROUND/AIM: Gemcitabine (GEM)-induced vascular pain often occurs in patients. A 5% glucose solution for the lyophilized formulation of GEM solvent is known to decrease the frequency of GEM-induced vascular pain compared with saline. In this study, we aimed to examine the availability of glucose for a liquid formulation GEM solvent for the prevention of GEM-induced vascular pain. PATIENTS AND METHODS: In total, 214 patients with bile tract or pancreatic cancer, who received GEM-containing regimens, were enrolled in this retrospective study. The patients were divided into a glucose group, which was administered the liquid formation GEM diluted with glucose, and a saline group. The frequency of GEM-induced vascular pain was compared between them. RESULTS: Glucose significantly decreased the frequency of GEM-induced vascular pain during the first GEM administration (36% vs. 55%, p=0.005). CONCLUSION: Switching the solution for liquid formulation GEM from saline to glucose significantly decreased the frequency of vascular pain.
  • Takayuki Daisho, Keisuke Kagami, Koujiro Yamazaki, Nobuhisa Ishiguro, Tsutomu Endo, Masahiko Takahata, Hisataka Suzuki, Mitsuru Sugawara, Yoh Takekuma
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2021年12月15日 [査読有り][通常論文]
  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Mitsuru Sugawara
    Scientific reports 11 1 23298 - 23298 2021年12月02日 [査読有り][通常論文]
     
    The potential of steroid sparing from day 2 onward is reported in anthracycline-containing regimens for breast cancer treatment. We evaluated whether the reduction of dexamethasone (DEX) dose from 9.9 to 6.6 mg on day 1 is possible in anthracycline-containing treatments. Patients receiving anthracycline-containing regimens were divided into control (9.9 mg DEX on day 1) and reduced (6.6 mg DEX on day 1) groups, and retrospectively evaluated. The complete response (CR) rate and the incidence and severity of nausea, vomiting, anorexia, and fatigue were evaluated. The CR rate in the acute phase (day 1) was 63.1% and 38.1% in the control and reduced groups, respectively, with significant difference (P = 0.01) between the groups. However, no difference was found in the delayed phase (days 2-7). The incidence of anorexia and vomiting during treatment was not statistically different. Severity of nausea tended to, but not statistically, worsen while anorexia significantly worsened in the reduced group. Multivariate analysis suggested that patients < 55 years, with non- or less-alcohol drinking habit (< 5 days/week), and administered reduced-DEX dosage on day 1, have a higher risk of acute nausea development. Thus, reducing day 1 DEX dose in anthracycline-containing regimens is not suitable for acute nausea management.
  • Ryusei Mikami, Shungo Imai, Mineji Hayakawa, Mitsuru Sugawara, Yoh Takekuma
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 2 199 - 205 2021年10月19日 [査読有り][通常論文]
     
    INTRODUCTION: The purpose of this study was to evaluate the clinical applicability of urinary creatinine clearance (CrCl) for determining the initial dose of vancomycin (VCM) in critically ill patients and to assess VCM trough plasma concentration/maintenance daily dose (C/D) ratio in patients with augmented renal clearance (ARC). METHODS: As the primary outcome measure, correlations between estimated renal function and the VCM C/D ratio were compared using the following formulas: CrCl, Cockcroft-Gault equation (eCrClC-G) and KineticGFR equation (KeGFR). Patients were divided into those with or without changes in renal function. The patients were further classified based on the presence or absence of ARC. The secondary outcome was the comparison of VCM C/D ratio between ARC and Non-ARC patients. RESULTS: A total of 65 patients were enrolled for analysis. In all groups, CrCl tended to correlate better with the VCM C/D ratio than eCrClC-G and KeGFR. A significantly lower VCM C/D ratio was observed in patients with persistent ARC than in the Non-ARC group (0.24 versus 0.52 kg/L). CONCLUSIONS: The clinical applicability of CrCl for the initial dosing design of VCM in critically ill patients was shown. Furthermore, the results indicated that patients with persistent ARC required a higher VCM dose than Non-ARC patients. Although our findings are limited, they have a value for further verification.
  • Shota Kadomura, Shungo Imai, Kenji Momo, Yuki Sato, Hitoshi Kashiwagi, Tatsuya Itoh, Mitsuru Sugawara, Yoh Takekuma
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 10781552211034703 - 10781552211034703 2021年10月18日 [査読有り]
     
    INTRODUCTION: Delayed methotrexate (MTX) clearance with the co-administration of piperacillin/tazobactam (PIPC/TAZ) has been reported. Penicillins have been associated with reduced MTX clearance but the evidence is limited. There are no cases described with cefepime but penicillins are listed as interacting with MTX. We aimed to reveal whether the co-administration of PIPC/TAZ or CFPM affects MTX clearance using data from an administrative database. METHODS: We used data from the JMDC database, a large insurance claims database constructed in Japan. We included patients who were prescribed PIPC/TAZ or CFPM between days 1 and 3 in high-dose MTX (HD-MTX). We compared one co-administration episode (with PIPC/TAZ or CFPM) to one control episode (without), as a match-control study of two different episodes in the same patient. The primary outcomes were the duration and cumulative dose of leucovorin (LV) as a surrogate indicator of delayed MTX clearance. RESULTS: Three patients who were co-administered PIPC/TAZ and 16 patients who were co-administered CFPM with HD-MTX were included. In the PIPC/TAZ group, the duration and the cumulative doses of LV were similar in co-administration and control episode (median 3.0 vs. 3.0 days and 288.0 vs. 219.0 mg). In the CFPM group, the duration and the cumulative doses of LV were not significantly different in co-administration and control episode (3.0 vs. 4.0 days and 169.5 vs. 258.0 mg). CONCLUSIONS: Our findings revealed that PIPC/TAZ did not necessarily cause a delay in MTX clearance during HD-MTX therapy. Moreover, the co-administration of CFPM with HD-MTX did not affect MTX clearance.
  • Yoshitaka Saito, Yoh Takekuma, Megumi Furuta, Mitsuru Sugawara
    Case Reports in Oncology 14 3 1418 - 1421 2021年10月04日 [査読有り][通常論文]
     
    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious adverse effects of chemotherapy. We experienced carboplatin (CBDCA)-induced akathisia-like CIPN, which was significantly attenuated by pregabalin administration, and report its treatment. A man in his 40s was administered CBDCA + pemetrexed (PEM) as the third-line treatment for recurrent malignant pleural mesothelioma. He rarely experienced mild akathisia-like symptoms on his feet before the diagnosis. The patient claimed that he exhibited mild degradation of the symptoms in the previous cisplatin (CDDP) + PEM treatment without the need for pharmacotherapy. Symptoms notably worsened approximately 7 days after the first cycle of CBDCA + PEM and did not disappear. Furthermore, symptoms worsened during the daytime and became milder at night. Lorazepam (0.5 mg) was administered 3 times a day from day 14 but was not effective. Finally, we evaluated the symptoms to be derived from CBDCA-induced neuropathy as he experienced the same symptoms in CDDP + PEM and did not have suspicious pathology or medicines for akathisia development. We decided to administer 75 mg pregabalin twice daily, resulting in significant symptom improvement. He also complained that he felt the symptoms 10 h after the previous pregabalin dose, suggesting that pregabalin was effective, and its effect weakened or disappeared as time progressed. Akathisia-like symptoms caused by CBDCA-induced CIPN are rare, but they significantly reduce the quality of life. Pregabalin was significantly effective in this case; therefore, we suggest that a detailed symptom interview and selection of the medicine, based upon the action mechanism, are necessary.
  • Takezo Tsutsumi, Shungo Imai, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Yoh Takekuma
    European journal of clinical pharmacology 78 2 279 - 286 2021年09月28日 [査読有り]
     
    PURPOSE: Some clinical studies have reported the occurrence of nausea and vomiting with linezolid (LZD) administration. However, no studies have evaluated nausea and vomiting as primary endpoints. In a previous study, we noted a possible relationship between LZD and vomiting, but risk factors were not identified. Therefore, the aim of the present study was to identify them. METHODS: Patients who received LZD 600 mg twice daily at Hokkaido University Hospital from September 2008 to April 2019 were enrolled in this retrospective observational study. Patient characteristics, concomitant medications, laboratory data, and the occurrence of vomiting were obtained from electronic medical records. Logistic regression analysis was performed to identify risk factors for vomiting, including age, sex, body weight, concomitant medications, and surgeries. RESULTS: A total of 496 patients were included in this study, of which 90 experienced vomiting. By multivariate logistic regression analysis, female sex (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.62-4.47), ≥ 10 days of LZD administration (aOR, 2.57; CI, 1.46-4.50), and hyponatraemia (aOR, 2.96; CI, 1.72-5.10) were identified as independent risk factors for vomiting; administration of serotonergic agents (aOR, 0.23; CI, 0.07-0.82) was negatively associated. CONCLUSIONS: This study is the first to successfully identify risk factors for LZD-induced vomiting. Careful monitoring of patients with these risk factors may lead to safer and sustainable LZD administration.
  • Yoshitaka Saito, Yoh Takekuma, Satoshi Takeuchi, Yoshito Komatsu, Mitsuru Sugawara
    International journal of clinical pharmacology and therapeutics 59 12 787 - 793 2021年09月10日 [査読有り]
     
    OBJECTIVE: We previously reported a case where S-1, containing tegafur, gimeracil, and oteracil potassium, induced severe hypertriglyceridemia. After the case, we regularly monitored serum lipid levels and surprisingly observed an additional 4 cases within 1.5 years. We here report the treatment process. CASE REPORT: At least 3 patients exhibited hyperlipidemia at baseline; in 2 of them, this was caused by previous fluoropyrimidine treatment. One patient experienced grade 4 hypertriglyceridemia, and the other 3 grade 3 hypertriglyceridemia. One patient developed temporary serum triglyceride elevation during the S-1 administration period, and the 3 experienced persistent elevation. The severity of serum triglyceride level worsened with increasing administration and peaked in cycles 2 - 6. Fenofibrate 80 - 160 mg/day and S-1 dose reduction were effective, with some significantly and others gradually decreasing to grade 0 - 1. DISCUSSION: The summarized clinical features are as follows: (1) Severe hypertriglyceridemia tends to appear after several treatment cycles and worsens with increasing administration. (2) It tends to occur in patients with hyperlipidemia at baseline. (3) Patients previously affected with fluoropyrimidines-induced hypertriglyceridemia can experience S-1 symptoms. (4) In some cases, it might decrease after the S-1 suspension period. (5) Fibrates and S-1 dose reductions were effective. As the final fluoropyrimidine product is fluorouracil, its presence or that of its metabolizing enzymes and the genetic background of the patients might have affected the results. We should be aware of the risk of temporal and asymptomatic occurrence of S-1-induced hypertriglyceridemia for early detection with appropriate treatment.
  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Mitsuru Sugawara
    Case Reports in Oncology 14 3 1277 - 1282 2021年09月09日 [査読有り][通常論文]
     
    Docetaxel (DOC) is one of the most effective agents for breast cancer treatment. Here, we report docetaxel-induced severe hypertriglyceridemia in a patient previously diagnosed with hyperlipidemia and corresponding therapeutic intervention. A postmenopausal woman, with previously controlled hyperlipidemia using rosuvastatin 5 mg daily, was diagnosed with stage IIB breast cancer with human epidermal growth factor receptor-2 overexpression; she received DOC (75 mg/m<sup>2</sup>), pertuzumab, and trastuzumab treatment as neoadjuvant chemotherapy. The serum triglyceride level was mildly higher than normal, and cholesterol level was normal at baseline. The serum triglyceride level was almost stable after chemotherapy initiation but suddenly increased to grade 3 (770 mg/dL) after the third cycle of the treatment without any symptoms. Sustained-release bezafibrate 400 mg was administered, resulting in a significant decrease to the baseline level; bezafibrate was discontinued on day 28 of the fourth chemotherapy as neoadjuvant chemotherapy was completed. The level was stable around the baseline level during adjuvant chemotherapy with pertuzumab and trastuzumab. Therefore, DOC-induced severe hypertriglyceridemia was strongly indicated in this case. The mechanism underlying the symptoms remains unclear; we speculate that it could be a resultant of a decrease in lipid metabolism as the patient had grade 2 diarrhea. Moreover, her backgrounds, such as mild hypertriglyceridemia, postmenopausal, diabetes, and obesity, in addition to DOC administration might have affected the outcome. Fibrate administration and cessation of treatment were as effective as in previous reports. DOC-induced hypertriglyceridemia presents with the possibility of severe complications. Elucidation of the exact mechanisms and epidemiological features is required for better management.
  • 宮井 貴之, 今井 俊吾, 百 賢二, 柏木 仁, 佐藤 夕紀, 菅原 満, 武隈 洋
    TDM研究 38 3 39 - 48 (一社)日本TDM学会 2021年09月 [査読有り][通常論文]
     
    ポリコナゾール(voriconazole;VRCZ)は深在性真菌症治療や造血幹細胞移植後の真菌症予防を目的に処方される。その有効性と副作用リスクは血漿中濃度に相関し、治療薬物モニタリング(therapeutic drug monitoring;TDM)が推奨されるが、処方患者数に対する実施割合の報告はない。そこで、大規模レセプトデータベースを利用し、患者数に基づくVRCZのTDM実施割合を特定薬剤治療管理料から評価した。ただし、VRCZ以外の算定対象薬を併用時、VRCZのTDMによる算定か否かを特定できないため、対象薬としてVRCZのみ処方された例(併用除外例)を評価した。2012年4月から2017年3月までにVRCZを処方された患者は417例、併用除外例は290例であった。併用除外例の32.8%、全例の37.4%でTDMが実施され、実施日の中央値はそれぞれ7日目、6日目であった。TDM実施に関連する要因として病棟薬剤業務、年齢、処方期間が見出された。TDM非実施例のうち、真にTDMの必要な患者がどの程度含まれているかを評価することが今後の課題である。(著者抄録)
  • Shungo Imai, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    British journal of clinical pharmacology 88 3 1211 - 1222 2021年08月26日 [査読有り][通常論文]
     
    AIMS: Musculoskeletal toxicity is a typical side effect of daptomycin (DAP). However, the risk factors have not been well established. Here, we aimed to identify independent factors affecting DAP-induced musculoskeletal toxicity using a combination of machine learning and conventional statistical methods. METHODS: A population-based, retrospective, observational cohort study was conducted using the Japanese electronic medical record database. Patients who received DAP between October 2011 and December 2020 were enrolled. Two definitions of musculoskeletal toxicity were employed: (1) elevation of creatine phosphokinase (CPK) value more than twice from baseline and > 200 IU/L, and (2) > 1,000 IU/L. First, multiple logistic regression analyses (a conventional statistical method) were performed to identify independent factors affecting CPK elevation. Then, decision tree (DT) analyses, a machine learning method, were performed to detect combinations of factors that change CPK elevation risk. RESULTS: Of the 2,970 patients who received DAP, 706 were included. Elevation of CPK values > 200 IU/L and > 1,000 IU/L occurred in 83 (11.8%) and 17 (2.41%) patients, respectively. In multiple logistic regression analysis, baseline CPK value and concomitant use of hydrophobic statins were commonly extracted as independent factors affecting each CPK elevation, but concomitant use of hydrophilic statins was not. In DT analysis, patients who received hydrophobic statins and had high baseline CPK values were classified into the high-risk group. CONCLUSIONS: Our novel approach revealed new risk factors for CPK elevation. Our findings suggest that high-risk patients require frequent CPK monitoring.
  • Keisuke Kagami, Nobuhisa Ishiguro, Takehiro Yamada, Yusuke Niinuma, Sumio Iwasaki, Keisuke Taki, Tatsuya Fukumoto, Kasumi Hayasaka, Mutsumi Nishida, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara, Yoh Takekuma
    American journal of infection control 49 12 1493 - 1498 2021年08月17日 [査読有り][通常論文]
     
    BACKGROUND: There are no reports on the effects of interventions, such as discontinuation and change/de-escalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. METHODS: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. RESULTS: Favorable clinical responses were obtained in 165/184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P=0.056). All-cause 30-day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P=0.045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P=0.026 for carbapenem; 10 days [5.3-15] versus 15.5 days [13.8-45.3], respectively, P=0.014 for anti-MRSA antibiotic). CONCLUSION: This is the first study to investigate the effects of interventions such as discontinuation and change/de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Expert opinion on drug safety 20 10 1 - 10 2021年07月19日 [査読有り]
     
    BACKGROUND: Hypernatremia and liver injury are typical adverse effects of tolvaptan. Therefore, hospitalization and frequent monitoring of serum sodium concentration and liver function are necessary for tolvaptan initiation. We performed a cross-sectional survey to evaluate these situations. RESEARCH DESIGN AND METHODS: We employed the Japanese claims database, which contains data of patients aged < 75 years. Patients who were newly prescribed tolvaptan for fluid accumulation induced by chronic heart failure (FA-CHF) or liver cirrhosis (FA-LC) from January 2011 to June 2017 were included. We evaluated the hospitalization status and implementation of serum sodium and liver function tests in the evaluation period, based on the Japanese package insert. RESULTS: Of 1,173 patients, 347 and 117 were enrolled in FA-CHF and FA-LC groups, respectively. Among them, 10.7% (FA-CHF group) and 5.13% (FA-LC group) were prescribed tolvaptan without hospitalization. In the FA-CHF group, 11.0% and 17.6% did not undergo serum sodium and liver function tests even once in the evaluation period, respectively, compared with 12.0% and 12.8% in the FA-LC group. CONCLUSIONS: Our results highlight the deviation from Japanese package insert recommendations. This approach can be applied to other drugs and provides important perspectives on pharmacovigilance research.
  • Yoshitaka Saito, Yoh Takekuma, Masaki Kobayashi, Tatsuhiko Sakamoto, Hiroko Yamashita, Mitsuru Sugawara
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2021年07月06日 [査読有り]
     
    PURPOSE: Taxane-associated acute pain syndrome (T-APS) reportedly occurs in approximately 70% of patients undergoing therapy. We have previously reported that additional dexamethasone (DEX) administration attenuates T-APS. The aim of this study was to reveal risk factor(s) associated with the incidence of T-APS under prophylactic DEX administration. METHODS: In total, 143 patients with breast cancer who received docetaxel (75 mg/m2) or paclitaxel (175 mg/m2)-containing treatment regimens were enrolled. DEX (4-8 mg) was orally administered on days 2-4. Risk factors for the incidence of ≥ G2 and all-grade T-APS, as well as T-APS incidence between taxane-containing regimens in the first cycle, were retrospectively evaluated. RESULTS: Approximately 90% of the patients received taxanes for adjuvant or neoadjuvant chemotherapy. Overall, 55% of patients administered 4 mg DEX, whereas 45% received 8 mg DEX. Pegfilgrastim was administered in 27% of patients. Incidence of ≥ G2 and all-grade T-APS was 23.8%, and 69.2%, respectively. Univariate and multivariate analyses revealed that administration of pegfilgrastim is an independent risk factor for the incidence of ≥ G2 and all-grade T-APS; age younger than 55 years is also a risk factor for all-grade T-APS. Moreover, the incidence of ≥ G2 and all-grade T-APS was 45.5% and 81.8% in a paclitaxel regimen, and 22.0% and 68.2% in docetaxel-including regimens, respectively, revealing increased tendency with paclitaxel administration, with no significant differences. CONCLUSION: Pegfilgrastim co-administration is an independent risk factor for ≥ G2 and all-grade T-APS, and age younger than 55 years is a risk factor of all-grade T-APS under prophylactic DEX administration.
  • Atsushi Yamaguchi, Yoshitaka Saito, Keisuke Okamoto, Katsuya Narumi, Ayako Furugen, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2021年06月23日 [査読有り]
     
    PURPOSE: Patients with preexisting autoimmune disease (PAD) are often excluded from clinical trials assessing immune checkpoint inhibitors (ICIs). Therefore, the safety of ICI therapy in patients with PAD remains unclear. Herein, we evaluated the incidence of immune-related adverse events (irAEs) in patients with PAD when compared with non-PAD patients. METHODS: We searched MEDLINE/PubMed, Web of Science, and Google Scholar for eligible studies from inception to January 2021. Observational studies reporting the incidence of irAEs in patients with and without PAD were included. We then performed a meta-analysis of eligible studies using forest plots. The primary endpoint of this study was the incidence rate of irAEs between patients with and without PAD. RESULTS: We identified three prospective and three retrospective studies involving 206 patients with PAD and 3078 patients without PAD. In the meta-analysis, 128 patients with PAD (62.1%) experienced irAEs, which occurred in 51.9% of non-PAD patients, resulting in an odds ratio (OR) of 2.14 (95% confidence interval [CI] 1.58-2.89). In the subgroup analysis, the incidence of irAEs was significantly higher in patients with PAD (OR = 2.19, 95% CI [1.55-3.08]). Furthermore, no significant heterogeneity or publication bias was detected, indicating that our meta-analysis could be generalized to clinical settings. CONCLUSION: This meta-analysis demonstrated that PAD was a risk factor for irAE incidence. These results suggest that monitoring the occurrence of irAEs in patients with PAD is required to manage irAEs appropriately.
  • Kazuki Uchiyama, Yoshitaka Saito, Yoh Takekuma, Satoshi Yuki, Mitsuru Sugawara
    Case Reports in Oncology 14 2 806 - 811 2021年06月10日 [査読有り]
     
    Irinotecan hydrochloride (irinotecan) is a chemotherapeutic agent used in the treatment of solid tumors. In addition to severe neutropenia and delayed diarrhea, irinotecan causes cholinergic syndrome, characterized by abdominal pain and acute diarrhea. The latter symptoms are frequently observed during and after irinotecan treatment. Here, we have discussed the case of a patient who completely recovered from abdominal pain following the administration of loperamide hydrochloride (loperamide) at a dose of 2 mg, before infusing irinotecan. In contrast, anticholinergic drugs were not as effective in alleviating symptoms. A 28-year-old man with stage IV rectal cancer with peritoneal metastasis was prescribed with fluorouracil, irinotecan, and levofolinate calcium (FOLFIRI), in addition to cetuximab. Anticholinergic drugs, such as scopolamine butylbromide (scopolamine) or atropine sulfate (atropine), were administered to treat abdominal pain that was considered as irinotecan-induced cholinergic syndrome, but monotherapy was not effective. Thereafter, oral loperamide (2 mg) with atropine (0.25 mg) was prescribed before irinotecan infusion. Consequently, the patient did not experience any abdominal pain during and after irinotecan treatment. Loperamide is an opioid receptor agonist and decreases the activity of the myenteric plexus of the intestinal wall. It also inhibits the release of both acetylcholine and prostaglandins, resulting in decreased inhibition of peristaltic movement. We assumed that its mechanism solely or in combination contributed to symptom relief. We hypothesized that the synergistic anticholinergic interaction between loperamide and atropine resulted in marked suppression of irinotecan-induced cholinergic syndrome compared to loperamide alone. Thus, loperamide may improve abdominal pain attributed to irinotecan-induced cholinergic syndrome.
  • Yuko Watanabe, Yoshitaka Saito, Takashi Mitamura, Yoh Takekuma, Mitsuru Sugawara
    Journal of pharmaceutical health care and sciences 7 1 21 - 21 2021年06月01日 [査読有り]
     
    BACKGROUND: Recently, aprepitant has been recommended in carboplatin-based regimens, but there are limited reports on the efficacy of administering aprepitant, palonosetron, and dexamethasone (DEX) in carboplatin-containing regimens. Moreover, because aprepitant is an expensive drug, confirming its effectiveness is very important from the medical cost perspective. In this study, we examined the efficacy of prophylactically administered aprepitant, palonosetron and DEX, in paclitaxel and carboplatin (TC) combination chemotherapy. METHODS: Patients with gynecologic cancer who were treated with paclitaxel (175 mg/m2) and carboplatin (area under the curve, AUC = 5-6) combination chemotherapy were retrospectively evaluated. The complete response (CR) rate, severity of nausea, and incidence of anorexia in the first course were compared between patients who did not receive aprepitant (control group) and those who received (aprepitant group). RESULTS: The 106 patients were divided into two groups, consisting of 52 and 54 the control and aprepitant groups, respectively, and the patient background showed no significant difference between both groups. The CR rate of the overall phase between the control and aprepitant groups was 73.1 vs. 74.1%, that in the acute phase was 98.1 vs. 100%, and in the delayed phase was 75.0 vs. 74.1%, respectively, without any significant difference. The severity of nausea and incidence of anorexia were also not significantly different between both groups. CONCLUSIONS: The results of the study suggest that adding aprepitant to palonosetron and DEX does not prevent carboplatin-induced nausea and vomiting in gynecologic cancer patients. Therefore, adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer.
  • Yoshitaka Saito, Yoh Takekuma, Masaki Kobayashi, Yoshito Komatsu, Mitsuru Sugawara
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 29 6 3277 - 3285 2021年06月 [査読有り]
     
    PURPOSE: The combination of gemcitabine (GEM) and nanoparticle albumin-bound paclitaxel (nab-PTX) is an effective chemotherapeutic regimen for locally advanced and metastatic pancreatic cancer. The dose-limiting toxicities (DLTs) of this treatment are sepsis and neutropenia, while the relative dose intensity (RDI) of GEM is approximately 75% and of nab-PTX is 70-80%. In this study, we evaluated the risk factor(s) regarding treatment suspension, which leads to reduction in the RDI of these agents, enabling appropriate schedule management. METHODS: Two hundred patients with pancreatic cancer who received GEM + nab-PTX were retrospectively investigated. Frequency and risk factor(s) of suspension of the treatment and grade 3/4 neutropenia in the first course were evaluated. RESULTS: The frequency of treatment suspension in the first course was 61%. The frequency of grade 3/4 neutropenia was 51%, while that of thrombocytopenia was 7.5%. The RDI was 78.0% for GEM and 77.7% for nab-PTX. Univariate and multivariate analyses to identify risk or preventive factors related to treatment suspension suggested that low platelet count at baseline was a risk factor, whereas dose reduction from the treatment initiation was a preventive factor. The most common cause of abeyance was grade 3/4 neutropenia (83.6%), the risk factors of which were low platelet count and age ≥ 65 years at baseline, while dose reduction was a preventive factor. CONCLUSION: We found that a low platelet level at baseline was a risk factor, whereas dose reduction from initiation was a preventive factor in regard to treatment suspension and severe neutropenia occurrence in GEM + nab-PTX treatment.
  • Yoshitaka Saito, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 27 4 1020 - 1025 2021年06月 [査読有り][通常論文]
     
    INTRODUCTION: S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride. CASE REPORT: A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. At the end of the S-1 administration period in every course, his serum triglyceride level was found to be elevated. Finally, it reached grade 4, without any symptoms of acute pancreatitis in the fifth course, and fenofibrate 80 mg once a day was administered.Management & outcome: Interestingly, the elevation spontaneously normalized without any pharmacotherapy 14 days after S-1 withdrawal, and this elevation did not occur when S-1 was not administered. Further, fenofibrate administration attenuated the hypertriglyceridemia to grades 1-3, with no complications. DISCUSSION: S-1 administration induced hypertriglyceridemia owing to the elevated serum triglyceride; however, a contrasting result was observed in the S-1 withdrawal period and during the S-1-cessation cycle. Since dietary intake was poorer during the S-1 administration period, it is considered that S-1 might have disturbed lipid metabolism. Further, we know that capecitabine, which is a prodrug of fluorouracil, also induces hypertriglyceridemia. As the end product of these medicines is fluorouracil, the presence of fluorouracil or its metabolizing enzymes, the genetic background of the patient might have affected the results. We have to be aware of the risk of asymptomatic and temporal occurrence of hypertriglyceridemia by S-1 administration for the early detection with appropriate pre-emptive treatment.
  • Ayako Nishimura, Ayako Furugen, Takeshi Umazume, Seika Kitamura, Mayuko Soma, Kiwamu Noshiro, Yoh Takekuma, Mitsuru Sugawara, Ken Iseki, Masaki Kobayashi
    Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine 16 5 424 - 431 2021年05月 [査読有り]
     
    Objective: Benzodiazepines are common therapies for mental illness and insomnia, and are used during pregnancy and lactation. Although benzodiazepines have been shown to be transferred into breast milk, the amount transferred is small and compatible with breastfeeding. However, information is not available for all drugs. Therefore, we aimed to determine the milk to plasma (M/P) ratio and relative infant dose (RID), which are used as indicators of drug transfer to breast milk, to determine the safety of such drugs for lactating women and breastfeeding infants. Methods: The study comprised of 11 pregnant women who visited the obstetrics department of Hokkaido University Hospital (approval number: 017-0131) and Tenshi Hospital (approval number: 103) for childbirth. The samples were analyzed using liquid chromatography-tandem mass spectrometry, and the M/P ratio and RID were calculated. The condition of the mother and baby at 1 month after delivery was determined from the clinical information. The target benzodiazepines were alprazolam, brotizolam, clonazepam, clotiazepam, etizolam, ethyl loflazepate, flunitrazepam, and lorazepam. Results: For all drugs, the M/P ratios were <1 and remained constant over time. For drugs other than ethyl loflazepate, the RID values were <10%, which are considered safe; however, even with ethyl loflazepate, it was only slightly >10%. No abnormalities were found in breastfeeding infants whose mothers were receiving these medications. Conclusions: The RID results of this study suggest that drug exposure through breast milk is small; thus, maternal drug treatment and breastfeeding are compatible.
  • Michiyo Tatsumi, Satomi Kumagai, Takahiro Abe, Soichi Murakami, Hiroshi Takeda, Toshiaki Shichinohe, Yuko Watanabe, Shinsuke Katayama, Shiaki Hirai, Aiko Honda, Yoh Takekuma, Mitsuru Sugawara
    Journal of pharmaceutical health care and sciences 7 1 16 - 16 2021年04月06日 [査読有り][通常論文]
     
    BACKGROUND: Several studies have reported the implementation of nutrition therapy and rehabilitation for acute and critical illnesses. However, rehabilitation nutrition for elderly sarcopenia patients with extremely severe postoperative complications during hospitalization has not yet been established. CASE PRESENTATION: We report the case of a 70-year-old man with sarcopenia that developed as a postoperative complication of the surgical resection of perihilar cholangiocarcinoma and left the patient bedridden from prolonged malnutrition and muscle weakness. The patient's general condition improved after a nearly 6-month intervention by our Nutrition Support Team (NST) that combined nutrition, exercise, and pharmacotherapy. CONCLUSIONS: The appropriate timing and order of pharmacotherapy, nutrient administration, exercise therapy, and team collaboration may enable elderly patients with severe (secondary) sarcopenia and postoperative complications to regain self-sustained walking.
  • 北海道大学病院における新型コロナウイルス感染症の流行に伴う職務上の影響にかかわる調査結果
    阿部 結希, 清水 薫子, 中司 展人, 船木 典子, 長堀 紀子, 菅原 満, 澁谷 斉, 高橋 久美子, 北川 善政, 今野 哲, 渥美 達也
    日本医師会雑誌 150 1 95 - 100 (公社)日本医師会 2021年04月 [査読有り][通常論文]
     
    新型コロナウイルス感染症(COVID-19)流行による業務への影響を把握し、今後の方策を提案することを目的とし、北海道大学病院に勤務する職員を対象に、2020年2月28日〜5月31日の業務についてアンケート調査を実施した。医育機関という観点から、診療・研究・教育という多面的な評価を行い、欠勤とその理由についても調査した。いずれの業務においても、多様な影響が見られた。欠勤はすべての職種に認められ、主な理由は、家族の一斉休校、休園や自粛要請であった。職場の雰囲気や理解、体制の構築を望む回答者が多く見られ、オンライン化や在宅・分散勤務、感染対策の徹底など、継続が有効と思われる変化も見られた。特に感染対策として、本人あるいは家族の体調不良時の欠勤、復職基準の徹底は重要であり、同時に職員がスムーズに出欠勤できる支援体制が必要と思われた。(著者抄録)
  • 窪田 篤人, 今井 俊吾, 百 賢二, 菅原 満, 武隈 洋
    薬局薬学 13 1 54 - 61 (一社)日本薬局学会 2021年04月 [査読有り]
     
    【背景】クローン病(CD)は,主として全消化管に非連続性の慢性肉芽腫性炎症などを生じる原因不明の炎症性疾患である.昨今,生体内利用率の低いブデソニド徐放性製剤(当製剤)が高い治療成績を収めているが,本邦における使用経験は少ないのが現状である.【目的】当製剤使用患者の併用薬,検査項目を抽出し,その特徴を明らかにすることを目的とした.【方法】JMDC Claims Databaseより2016年11月から2017年6月30日までにCDと診断された患者のうち,当製剤を処方された患者51名を抽出した.【結果・考察】当製剤使用患者は,使用前に比べ5-ASA,PSLの使用率が低く,他剤無効による治療薬変更の可能性が示された.また,B型肝炎ウイルス(HBV)再活性化リスク患者(N=41)のうち,HBs,c抗体検査の頻度が少なく(N=17),適切な検査が行われていない可能性が示された.(著者抄録)
  • 今井 俊吾, 難波 正志, 柏木 仁, 佐藤 夕紀, 武隈 洋, 菅原 満
    薬局薬学 13 1 68 - 78 (一社)日本薬局学会 2021年04月 [査読有り]
     
    薬剤師は安全な薬物療法の提供のために,患者から必要な情報を「聞き取る」ことが重要である.しかし,薬局薬剤師の「聞き取り」に対し,一部の一般市民は厳しい視線を投げかけており,患者の理解を促すためのエビデンス構築が急務である.本研究は「患者への聞き取り」に基づき実施された疑義照会に着目し,その実態解明と医療安全への貢献度評価を試みた.解析には北海道大学病院の近隣薬局の疑義照会データを用いた.その結果,聞き取りに基づく疑義照会は「薬学的疑義照会の33.3%を占め,高い許諾割合(98.5%)を有し,用法や用量などの疑義照会分類において,医療安全への貢献度が高い」ことが見いだされた.また,このうち「医師からの説明と処方内容が食い違う」ことが発端となった事例が,特に医療安全へ貢献していることが示された.「患者への聞き取り」に基づく疑義照会の有用性を広く調査するための基礎となる知見が創出された.(著者抄録)
  • Keisuke Kagami, Nobuhisa Ishiguro, Takehiro Yamada, Yusuke Niinuma, Sumio Iwasaki, Keisuke Taki, Tatsuya Fukumoto, Kasumi Hayasaka, Reiko Oyamada, Tsubasa Watanabe, Mutsumi Nishida, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara, Yoh Takekuma
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 3 473 - 479 2021年03月 [査読有り]
     
    BACKGROUND: The efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli have been poorly investigated in Japanese patients. This study was performed to investigate the efficacy and safety of colistin in Japanese patients by analyzing a considerable number of cases. Furthermore, we evaluated the relationship between the plasma concentration and efficacy and safety of colistin in some cases. METHODS: A retrospective cohort study was conducted at Hokkaido University Hospital, analyzing patients treated with colistin (colistimethate sodium) during the period from January 2007 to December 2019. RESULTS: Overall, 42 cases were enrolled. Favorable clinical response was observed in 25 cases (59.5%), with an all-cause 30-day mortality of 33.3% (14/42 cases). Microbiological eradication was achieved in 18 cases (42.9%). Nephrotoxicity was observed in 20 cases (47.6%) and was mild and reversible in all cases. Plasma trough concentrations of colistin determined in nine patients correlated with changes in serum creatinine concentration (⊿) and creatinine clearance (%). The cutoff value of colistin trough concentration for nephrotoxicity was 2.02 μg/mL. CONCLUSION: Our results showed approximately 60% clinical efficacy of colistin therapy against infections caused by multidrug-resistant gram-negative bacilli in the patients. Further studies with larger populations are needed to elucidate the efficacy and safety of colistin in Japanese patients.
  • Yoshitaka Saito, Yoh Takekuma, Masaki Kobayashi, Naofumi Shinagawa, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Ken Iseki, Mitsuru Sugawara
    European journal of clinical pharmacology 77 3 381 - 388 2021年03月 [査読有り][通常論文]
     
    PURPOSE: Gefitinib is one of the standard treatments for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations. It has been reported that acid suppressants (AS) decrease the anti-tumor effect of gefitinib by reducing its solubility. AS is sometimes necessary in cancer patients; however, previous reports have not shown the most compatible AS with gefitinib administration in cancer patients. This study was conducted to determine if histamine type 2 receptor antagonists (H2RAs) can affect the anti-tumor efficacy of gefitinib. METHODS: Eighty-seven patients with NSCLC who were administered gefitinib were retrospectively investigated. Patients who were co-administered H2RA were compared with non-AS control patients. H2RA was administered once a day at about 3-5 or 8-12 h after gefitinib intake. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR), and adverse effects. RESULTS: Median PFS in H2RA group and control group was 8.0 months and 9.0 months, respectively, with no significant difference (p = 0.82). The incidence of liver dysfunction was significantly less in patients administered H2RA, whereas there were no differences between the two groups with regard to skin toxicity and diarrhea. Multivariate analysis suggested that H2RA co-administration is not a risk factor for worse PFS and OS (hazard ratio of 0.95, 0.86; 95% confidence interval of 0.60-1.48, 0.52-1.43; p = 0.82 and 0.60, respectively). CONCLUSION: This study demonstrated that concomitant administration of H2RA with gefitinib does not affect the efficacy of gefitinib.
  • Shunsuke Nashimoto, Saori Yagi, Naoki Takeda, Miku Nonaka, Yoh Takekuma, Mitsuru Sugawara, Yuki Sato
    Biochimica et biophysica acta. Biomembranes 1863 2 183508 - 183508 2021年02月01日 [査読有り]
     
    Niemann-Pick C1 Like 1 (NPC1L1) is known to be involved in the intestinal absorption of cholesterol. For evaluating the function of NPC1L1, cell lines such as Caco-2, Madin-Darby canine kidney (MDCK) II, and McA-RH7777 have been used in previous studies, but the detailed molecular mechanism of transport has not been elucidated. In this study, the characteristics of cholesterol transport via NPC1L1 were investigated using a Xenopus laevis oocyte expression system in addition to a conventional cell line with stable expression. The transport activity of cholesterol uptake was increased in NPC1L1-overexpressed MDCK cells compared with that in mock cells, but MDCK cells expressed endogenous NPC1L1 and had high cholesterol transport activity. On the other hand, cRNA-injected oocytes expressed NPC1L1 after culturing for 5-6 days. The transport activity of cholesterol uptake was increased in NPC1L1 cRNA-injected oocytes compared with that in water-injected oocytes. In addition, the uptake of cholesterol was decreased in the presence of ezetimibe, an NPC1L1 inhibitor, in cRNA-injected oocytes but not in control oocytes, indicating that endogenous NPC1L1 is not expressed in oocytes. Furthermore, cholesterol uptake was substantially decreased in NPC1L1 L216A cRNA-injected oocytes compared with that in NPC1L1 cRNA-injected oocytes, indicating that leucine at position 216 of NPC1L1 is important for cholesterol transport and that an oocyte expression system is useful for mutant analysis. These results indicate that the oocyte expression system is useful for evaluating the characteristics of NPC1L1-mediated cholesterol transport and may contribute to the elucidation of the detailed molecular mechanism of cholesterol transport via NPC1L1.
  • Yoshitaka Saito, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 44 12 1819 - 1823 2021年 [査読有り][通常論文]
     
    We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.
  • Yoshitaka Saito, Yoh Takekuma, Satoshi Yuki, Yoshito Komatsu, Mitsuru Sugawara
    Case Reports in Oncology 14 1 207 - 211 2021年01月 [査読有り]
     
    We had previously reported on S-1-induced hypertriglyceridemia. Here, we report fluorouracil-induced hypertriglyceridemia in a patient with capecitabine-induced hypertriglyceridemia and the corresponding therapeutic process. A woman in her forties who had experienced grade 3 hypertriglyceridemia due to oxaliplatin + capecitabine was administered fluorouracil ± oxaliplatin + levofolinate calcium + panitumumab; however, grade 4 hypertriglyceridemia occurred after the thirteenth administration. Bezafibrate normalized the elevation. Chemotherapy cessation resulted in its decrease to normal, and bezafibrate was stopped. Nine months after cessation, treatment with fluorouracil + irinotecan + levofolinate calcium + ramucirumab was initiated. After four cycles of treatment, her serum triglyceride levels increased again to grade 3, and then, fenofibrate was administered, resulting in a significant decrease to grade 1-2. Serum triglyceride levels significantly reduced after cessation of the prior fluorouracil-containing regimen, although its elevation was observed again following the latter treatment. Therefore, fluorouracil-induced hypertriglyceridemia was strongly speculated in this case. We have speculated that the most probable cause of tegafur and capecitabine-induced hypertriglyceridemia is fluorouracil or its metabolic enzymes since their end product is fluorouracil in the previous report. Results from this patient suggest that our supposition was correct. Fibrates administration, cessation of the treatment, and monitoring of serum triglyceride level was effective in this case as well as previous reports. Fluorouracil-induced hypertriglyceridemia is associated with the one caused by tegafur and capecitabine and presents the possibility of severe complications. Elucidation of its exact mechanism and epidemiological features is needed for better understanding.
  • Shungo Imai, Yasuyuki Nasuhara, Kenji Momo, Hiromitsu Oki, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 44 10 1499 - 1505 2021年 [査読有り]
     
    A major adverse effect of benzbromarone is hepatotoxicity. Therefore, periodic liver function tests are required at least for the first 6 months of benzbromarone administration. However, it is not clear whether the relevant blood tests are implemented appropriately. Here, we performed a cross-sectional survey of the implementation status of liver function tests in patients who were newly prescribed benzbromarone, using the Japanese large claims database. Male patients who were newly prescribed benzbromarone from January 2010 to December 2016 were included. We targeted patients who continued benzbromarone during the observation period (up to 180 d from the start of administration). The primary endpoint was the proportion of patients in whom periodic liver function tests were implemented. A periodic liver function test was defined as one or more liver function tests performed during both 1-90 and 91-180 d of initial benzbromarone administration. We labeled the tests as a "periodic test" or "non-periodic test" based on whether periodic liver function tests were performed or not, respectively. Furthermore, factors influencing non-periodic test were analyzed. Periodic testing was implemented only in 28.7% of patients. Additionally, factors such as number of hospital beds ≤19 (compared to 100-199 beds) and duration of the first prescription of benzbromarone were associated with non-periodic testing. Our study revealed that periodic liver function tests are not performed sufficiently in Japan. Thus, clinicians prescribing benzbromarone should be educated about the test. Our blood-test-based approach should be applied to other drugs and countries in future research.
  • Tsuyoshi Aoyama, Hiroki Kuriyama, Yuki Sato, Shungo Imai, Hitoshi Kashiwagi, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 44 8 1101 - 1110 2021年 [査読有り][通常論文]
     
    Dasatinib is a first-line pharmacotherapeutic treatment for chronic myeloid leukemia (CML). It is more effective than traditional treatments but causes adverse effects such as pleural effusion that limits its effective treatment cycle. Since pleural effusion is caused by vascular hyperpermeability and causes discontinuation of treatment with dasatinib, it is important to explore the mechanism of pleural effusion caused by dasatinib and how to prevent it. In this study, we investigated how dasatinib increase vascular permeability, and how it can be prevented. Cytotoxicity was observed in vascular endothelial cells or epithelial cells were exposed to high concentrations of dasatinib. Thus, it was observed in vascular endothelial cells such as human umbilical vascular endothelial cell (HUVEC). Vascular endothelial (VE)-cadherin is one of the important factors that control vascular permeability. When VE-cadherin expression decreases, vascular permeability increases, but it did not change with tyrosine kinase inhibitor exposure. Monolayer permeability significantly increased only with high concentration of dasatinib, but this increase was prevented by cAMP activation. Furthermore, dasatinib affects the cell morphology of HUVEC, with increased inter celluar space compared to control and bosutinib, which were also attenuated by cAMP activation. Dasatinib significantly affected permeability control of vascular endothelial cells compared to bosutinib and imatinib. These results indicated that the cAMP signaling pathway may be involved in the pleural effusion caused by dasatinib in CML patients.
  • Shinsuke Yamashita, Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 44 8 1151 - 1155 2021年 [査読有り][通常論文]
     
    Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.
  • Yoshitaka Saito, Kazuki Uchiyama, Tatsuhiko Sakamoto, Kojiro Yamazaki, Kosei Kubota, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 141 8 1023 - 1030 2021年 [査読有り][通常論文]
     
    Denosumab is a fully monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL), and prevents skeletal-related events by bone metastasis. Hypocalcemia is the most typical adverse effect of denosumab use. We have developed a management system for the more efficient and safer management of denosumab administration, and evaluated pharmaceutical interventions for the better control of hypocalcemia. All pharmaceutical interventions in the system from April 2016 to March 2020 were retrospectively evaluated. We have also assessed the incidence of hypocalcemia in 158 patients who were administered denosumab for six months or more in the period. A total of 282 pharmaceutical interventions (7.0% of the total administration) were conducted. The most conducted intervention was regarding hypocalcemia, which involved the suspension of the injection and/or the increase of calcium and vitamin D supplement with 65% adoption and 17% temporary treatment suspensions. Other interventions were about hypercalcemia, request of laboratory examination and ordering supplements, dental consultation, and poor renal function. A total of 199 interventions (70.6%) were adopted, with 33 administrations suspended. The frequency of hypocalcemia was 27.8% with just one patient having grade 2 hypocalcemia, suggesting that there were no severe cases. Moreover, hypocalcemia was significantly normalized following pharmaceutical intervention and/or handling by physicians (p=0.02) according to the system. Conversely, the normalization rate in hypercalcemia did not differ according to the countermeasures. In conclusion, pharmaceutical interventions according to our management system benefit safe denosumab treatment, especially in severe hypocalcemia prevention.
  • Yuki Sato, Kazuki Yamaguchi, Mikako Ogawa, Yoh Takekuma, Mitsuru Sugawara
    PloS one 16 6 e0253066  2021年 [査読有り][通常論文]
     
    BACKGROUND & OBJECTIVE: Theanine (L-glutamylethylamide) contained in green tea is a functional food component that has been attracting attention due to its relaxation effect. It was shown that the ingredients added to the theanine formulations increased the absorption of theanine. If this mechanism can be elucidated, it would be possible to contribute to development of evidence-based formulations. In this study, we investigated the effect of ingredients in the formulations on the absorption of theanine in detail. MAIN METHODS: After oral administration of a mixture of theanine and additional components to Wistar rats the plasma concentration was determined by an HPLC and the pharmacokinetic parameters were calculated. In addition, a new system for evaluating intestinal blood flow was developed since the involvement of intestinal blood flow was considered as a factor that increased absorption of theanine. KEY FINDINGS: Plasma concentration of theanine increased significantly in the combined use group with eight ingredients containing piperine as compared with theanine only group. Piperine would increase theanine absorption by increased blood flow, not an inhibition of metabolism. We succeeded to develop a visual and quantitative system to evaluate the effect of these ingredients directly including piperine on the intestinal blood flow using indocyanine green while maintaining physiological conditions. SIGNIFICANCE: Increased intestinal blood flow by these ingredients including piperine enhanced the absorption of theanine. Other mechanisms may also be considered as the mechanism by which theanine absorption is increased in addition to increased blood flow.
  • Yoshitaka Saito, Shinya Tamaki, Haruka Hasegawa, Kenta Takahashi, Akira Tokutome, Yoh Takekuma, Hiroko Yamashita, Yoshito Komatsu, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 44 4 474 - 477 2021年 [査読有り][通常論文]
     
    CT-P6 is a biosimilar of trastuzumab and is recommended to be administered for 30-90 min in subsequent maintenance infusions to prevent infusion-related reactions (IRRs). We administered CT-P6 for 30 min as the first injection and as an alternative to reference trastuzumab in the maintenance infusion and evaluated the safety of the administration. A total of 140 patients with breast or gastric cancer, who received a switch from tri-weekly reference trastuzumab to CT-P6 for 30 min in maintenance infusions, were retrospectively evaluated. Premedication was administered prior to an infusion of CT-P6 and a cytotoxic agent. However, premedication was not provided when CT-P6 was co-administered with pertuzumab or administered alone. The primary endpoint was the incidence of IRRs. The secondary endpoint was the incidence of diarrhea and skin toxicity. Ninety-five percent of the patients had breast cancer, and 44.3% had advance-stage cancer. The treatment included CT-P6 alone (17.9%) or with cytotoxic agents (23.6%), antihormonal drugs (25.7%), and pertuzumab (62.9%). Median administration time of trastuzumab at the switch was 13 administrations (range 2-140). Premedication was administered to 20.7% patients. One patient (0.7%) experienced grade 3 IRR. The frequency of diarrhea in the reference trastuzumab group and the CT-P6 group was 7.1 and 6.4%, respectively, and that of skin toxicity was 6.4 and 5.0%, respectively, without differences. In conclusion, we first demonstrated that an initial CT-P6 administration for 30 min during the switch from reference trastuzumab in maintenance infusion is an acceptable administration method.
  • Masayoshi Kumai, Shungo Imai, Shintaro Kato, Ryo Koyanagi, Kenkichi Tsuruga, Takehiro Yamada, Yoh Takekuma, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 44 4 593 - 598 2021年 [査読有り][通常論文]
     
    Nausea is a typical adverse event associated with opioids. In this study, we performed logistic regression analysis with the aim of clarifying the risk factors for nausea induced by extended-release oxycodone (ER-OXY). Furthermore, we constructed a decision tree (DT) model, a typical data mining method, to estimate the risk of oxycodone-induced nausea by combining multiple factors. A retrospective study was conducted on patients who newly received ER-OXY for cancer pain during hospitalization at Hokkaido University Hospital in Japan from April 2015 to March 2018. In logistic regression and DT analyses, the dependent variable was the presence or absence of nausea. Independent variables were the potential risk factors. First, univariate analyses were performed to screen potential factors associated with oxycodone-induced nausea. Then, multivariate and DT analyses were performed using factors with p-values <0.1 in the univariate analysis. Of 267 cases included in this study, nausea was observed in 30.3% (81/267). In multivariate logistic regression analysis, only female sex was extracted as an independent factor affecting nausea (odds ratio, 1.98). In the DT analysis, we additionally revealed that an age <50 years was a risk factor for nausea in female patients. Thus, our DT model indicated that the risk of ER-OXY-induced nausea was highest in the subgroup comprising females <50 years of age (66.7%) and lowest in male patients (25.1%). The DT model suggested that the factor of young women may be an increased risk of ER-OXY-induced nausea.
  • Yoshitaka Saito, Kazuki Uchiyama, Tatsuhiko Sakamoto, Kosei Kubota, Hiromitsu Oki, Miwako Iwai, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 44 3 293 - 297 2021年 [査読有り][通常論文]
     
    Chemotherapy regimen management is one of the most important oncology pharmacy practices, because chemotherapy is conducted according to the registered regimens. In this study, we evaluated the pharmaceutical practice that assumes the initial confirmation of chemotherapy regimens and the quality of practice sharing between oncology-specialized and non-specialized pharmacists in regimen management committee. Pharmacists initially confirmed the applied regimen prescribed by physicians regarding chemotherapeutic agents and prophylactic supportive care medicines. Following confirmation, the regimens were reviewed by the Hokkaido University Hospital Regimen Management Committee. A total of 233 regimens were reviewed by the committee over three years. In total, 110 pharmaceutical inquiries were conducted, 45% of inquiries were concerning chemotherapeutic agents, of which approximately half were regarding supportive care medicines. Most inquiries were regarding premedication, followed by those on administration time, solvent of infusion medicines, and dosage. Correction was performed for 84.5% of inquiries. There was no significant difference in inquiry rates between practice and trial regimens. We have entrusted the first basic regimen review according to the checklist, creation of the chemotherapy plan document, and registry of the adopted regimens in the ordering system from oncology-certified pharmacists to non-certified pharmacists. Basic regimen review was well conducted by a non-certified pharmacist, and a more advanced review was additionally performed by certified pharmacists. In conclusion, we demonstrated the utility of pharmaceutical confirmation in a chemotherapeutic regimen review, suitable review coverage, and quality practice sharing between oncology-certified and non-certified pharmacists, which is one of the recommended methods in chemotherapy regimen review.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 44 3 448 - 452 2021年 [査読有り][通常論文]
     
    Antibiotic-associated diarrhea (AAD) is a typical side effect of antibiotic treatment, especially in children. Amoxicillin (AMPC) and amoxicillin/clavulanate (AMPC/CVA) are associated with high risk of AAD; however, these antibiotics are important in the pediatric field. Recent research suggests that probiotics prevent pediatric AAD, including that caused by AMPC and AMPC/CVA. Indeed, guidelines for acute otitis media in children recommend the concomitant use of probiotics. However, the prescription status of probiotics for pediatric patients with otitis media receiving oral AMPC and AMPC/CVA remains unknown. We therefore conducted a survey to clarify the current status of these prescriptions and, in particular, to identify specific populations with a low proportion of probiotic prescriptions. Pediatric patients (≤15 years of age) newly prescribed oral AMPC or AMPC/CVA for otitis media between April 2016 and March 2017 were identified from a Japanese health insurance claims database. Eligible patients were divided into the AMPC (1303 patients) and AMPC/CVA (424 patients) groups, in which 659 (50.6%) and 293 (69.1%) patients were prescribed probiotics, respectively. Of the patients receiving probiotic prescriptions in the AMPC and AMPC/CVA groups, 632 (95.9%) and 286 (97.6%) patients received antibiotic-resistant probiotic prescriptions, respectively. When classified by the prescribing clinical department and patient age, the proportions of probiotic prescriptions in Internal Medicine and Pediatrics departments were lower than those in the Otorhinolaryngology department regardless of age. These results indicate the probability of insufficient probiotic prescriptions for pediatric patients with otitis media. Solving this issue may lead to the provision of safer antimicrobial therapy.
  • Kazuki Uchiyama, Yoshitaka Saito, Yoh Takekuma, Junichi Sugita, Takanori Teshima, Mitsuru Sugawara
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 1078155220980815 - 1078155220980815 2020年12月22日 [査読有り][通常論文]
     
    PURPOSE: Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, is used to prevent graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). Although previous studies have reported that enterohepatic circulation (EHC) of MPA, which is usually observed in MMF-treated patients, does not occur in HSCT patients, it is unclear what happens in haploidentical-HSCT (haplo-HSCT) patients, who are using post-transplant cyclophosphamide. This study was conducted to investigate MPA pharmacokinetics in haplo-HSCT patients. METHODS: Seventeen haplo-HSCT patients, who received MMF for GVHD prophylaxis, were enrolled in this study. We collected blood samples on days 14 and 28, and plasma MPA concentrations were measured by high-performance liquid chromatography; pharmacokinetic parameters such as area under the curve (AUC), mean residence time (MRT), and apparent oral clearance (CL/F) were measured with moment analysis. We also evaluated EHC as AUC6-12h/AUC0-12h. RESULTS: There was no significant difference in MPA pharmacokinetic parameters between days 14 and 28. There was also no difference between the pharmacokinetic parameter changes and diarrhea. Additionally, varying plasma MPA concentrations suggested that MPA EHC did not occur. CONCLUSION: In this study, we revealed the pharmacokinetics of MMF in Japanese haplo-HSCT recipients. Additionally, our study demonstrated that MPA EHC might not occur in Japanese haplo-HSCT recipients.
  • Takayuki Miyai, Shungo Imai, Hitoshi Kashiwagi, Yuki Sato, Shota Kadomura, Kenji Yoshida, Eri Yoshimura, Toshiaki Teraya, Takashi Tsujimoto, Yukari Kawamoto, Tatsuya Itoh, Hidefumi Ueno, Yoshikazu Goto, Yoh Takekuma, Mitsuru Sugawara
    Antibiotics (Basel, Switzerland) 9 12 1 - 12 2020年12月18日 [査読有り][通常論文]
     
    We previously constructed a risk prediction model of vancomycin (VCM)-associated nephrotoxicity for use when performing initial therapeutic drug monitoring (TDM), using decision tree analysis. However, we could not build a model to be used at the time of initial administration due to insufficient sample size. Therefore, we performed a multicenter study at four hospitals in Japan. We investigated patients who received VCM intravenously at a standard dose from the first day until the initial TDM from November 2011 to March 2019. Acute kidney injury (AKI) was defined according to the criteria established by the "Kidney disease: Improving global outcomes" group. We extracted potential risk factors that could be evaluated on the day of initial administration and constructed a flowchart using a chi-squared automatic interaction detection algorithm. Among 843 patients, 115 (13.6%) developed AKI. The flowchart comprised three splitting variables (concomitant drugs (vasopressor drugs and tazobactam/piperacillin) and body mass index ≥ 30) and four subgroups. The incidence rates of AKI ranged from 9.34 to 36.8%, and they were classified as low-, intermediate-, and high-risk groups. The accuracy of flowchart was judged appropriate (86.4%). We successfully constructed a simple flowchart predicting VCM-induced AKI to be used when starting VCM administration.
  • 小林 洋平, 山岡 怜央, 三上 龍生, 山崎 浩二郎, 熊井 正貴, 山田 武宏, 武隈 洋, 菅原 満, 井関 健
    日本臨床救急医学会雑誌 23 6 771 - 779 (一社)日本臨床救急医学会 2020年12月 [査読有り][通常論文]
     
    目的:救急/集中治療室(以下、ICU)における薬剤師介入の実態や医療経済効果を明らかにすることを目的とした。方法:2017年7、8月に、救急科に入院した患者を対象とし、疑義照会記録を用いて後方視的に調査した。薬学的知識を要しない介入を単純エラー、薬学的知識を要する介入を薬学的介入と定義し、介入の内容および処方反映率を調査した。また、能動的な薬学的介入(薬剤師からの提案)に関して医療経済効果を算出した。結果:介入は391件あり、そのうち76%(297件)が薬学的介入であった。薬学的介入では、抗微生物薬関係の介入がもっとも多く117件(反映率91%)であった。また、医療経済効果は、2ヵ月間で3,832,000円であった。結論:薬剤師の救急/ICUへの参画は、医療経済的に有益であることが明らかとなった。また抗微生物薬関係の介入が多く、今後プロトコル作成などにより適正使用推進に寄与できると示唆された。(著者抄録)
  • オピオイド使用患者の眠気に対する安息香酸ナトリウムカフェイン散の効果
    熊井 正貴, 山田 武宏, 敦賀 健吉, 武隈 洋, 菅原 満
    日本緩和医療薬学雑誌 13 4 119 - 125 (一社)日本緩和医療薬学会 2020年12月 [査読有り][通常論文]
     
    安息香酸ナトリウムカフェイン散は眠気、倦怠感の適応を有するが、オピオイド使用患者における眠気改善には十分なエビデンスがない。われわれは、オピオイド使用患者の眠気に対する安息香酸ナトリウムカフェイン散の効果を検証するために後ろ向きカルテ調査を行った。眠気はNumeric Rating Scale(NRS)、Epworth Sleepiness Scale日本語版(JESS)を用いて評価し、倦怠感もNRSを調査した。調査対象4例すべてで眠気NRS(0〜10)は1〜5ポイント、JESSスコア(24点満点)は2〜14点の低下がみられた。倦怠感NRS(0〜10)は1例で5ポイント、1例で3ポイントの低下がみられたが、2例は不変であった。1例はせん妄、1例はイレウスにより休薬した。安息香酸ナトリウムカフェイン散は安全性に関して検証を行う必要があるが、オピオイド使用患者の眠気に対して有効である可能性が示された。(著者抄録)
  • Shunsuke Nashimoto, Yuto Takekawa, Yoh Takekuma, Mitsuru Sugawara, Yuki Sato
    Drug metabolism and pharmacokinetics 35 6 527 - 533 2020年12月 [査読有り][通常論文]
     
    Ubiquinone, which is a component in the electron-transport systems of mitochondria, is essential for various activities related to energy metabolism, but the detailed absorption mechanism of ubiquinone is not clear. On the other hand, Niemann-Pick C1 Like 1 (NPC1L1) is involved in the intestinal absorption of fat-soluble components such as cholesterol. In this study, we investigated whether the intestinal absorption of ubiquinone was transported by NPC1L1 as is cholesterol. In this study, coenzyme q10 (CoQ10) and coenzyme q9 (CoQ9) were used as models of ubiquinone. The transport activity of ubiquinone was increased significantly in NPC1L1-overexpressed Madin-Darby canine kidney (MDCK) cells compared with that in pMAM2-BSD vector-transfected MDCK cells and the uptake of ubiquinone was decreased in the presence of ezetimibe, an inhibitor of NPC1L1. These results indicate that NPC1L1 mediates the transport of ubiquinone. Furthermore, to clarify the effect of NPC1L1 on the intestinal absorption of CoQ10, emulsified CoQ10 was orally administered to Wistar rats, and the plasma concentration was measured. The plasma concentration of CoQ10 was significantly decreased by coadministration of ezetimibe and CoQ10 compared to that with administration of only CoQ10. This result indicates that the intestinal absorption of CoQ10 is mediated by NPC1L1.
  • Shungo Imai, Shota Kadomura, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 26 11 1224 - 1228 2020年11月 [査読有り][通常論文]
     
    Cephalosporins with an N-methyl-thio-tetrazole (NMTT) side chain interact with warfarin by reducing the production of blood clotting factors. However, cephalosporins without the NMTT side chain also enhance the effects of warfarin. Thus, we aimed to compare the effects of warfarin modified by cephalosporins with and without the NMTT side chain, using a Japanese health insurance claims database. The inclusion criteria were patients who (1) intravenously received second- or third-generation cephalosporins between April 2010 and March 2017 and (2) received warfarin during cephalosporin therapy. Patients were administered either cephalosporins with the NMTT side chain (NMTT group) or those without NMTT (non-NMTT group). After matching patient data by propensity score, the following outcomes were compared between the two groups: (1) proportion of patients administered vitamin K, (2) proportion of bleeding events, and (3) changes in the daily dose of warfarin. Among 203 patients, 100 patients (50 per group) were matched by the propensity score. The proportion of patients administered vitamin K was 6.0% in both groups. These patients intravenously received a single dose of menatetrenone; no bleeding was observed. The proportion of patients subjected to a reduction in the daily dose of warfarin was 6.5% and 4.3% in the NMTT and non-NMTT groups, respectively. As our study had a small sample size, we could not determine whether the risk of over anticoagulation of warfarin is affected by cephalosporins with or without NMTT side chain. However, we showed the bleeding risk was sufficiently low regardless of the presence/absence of the NMTT side chain.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    International journal of clinical pharmacy 42 5 1369 - 1373 2020年10月 [査読有り][通常論文]
     
    Background The concurrent use of nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system blockers, and diuretics, known as a "triple-whammy," is related to the occurrence of acute kidney injury. However, there are few reports regarding the prescription pattern of the triple-whammy. Objective To elucidate the patterns of the triple-whammy prescription in Japan. Methods A cross-sectional study was performed using a health-insurance-claims database that included Japanese people under 75 years of age, and enrolled outpatients that were prescribed any nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system blockers, and diuretics between April 2017 and June 2017. As an outcome, the proportion of triple-whammy prescriptions was evaluated. Among the patients who received triple-whammy prescriptions, we evaluated the prevalence of chronic kidney disease and the proportion of prescriptions provided for these three drugs from different clinical departments and institutions. Results Overall, 730 of 246,721 (0.3%) patients received triple-whammy prescriptions. Among these patients, 13.3% had underlying chronic kidney disease. The proportions of any of the three drug types prescribed by different clinical departments and institutions was 48.2% and 61.8%, respectively. Conclusions We examined the patterns of triple-whammy prescriptions and concluded that pharmacists need to pay attention to triple-whammy prescriptions if the prescriptions are provided by multiple clinical departments or institutions.
  • Yuki Sato, Tatsuru Joumura, Yoh Takekuma, Mitsuru Sugawara
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 154 210 - 213 2020年09月 [査読有り][通常論文]
     
    Hyaluronan (HA) has been widely used in medicines, cosmetics and supplements for health and beauty maintenance. Oral administration is the most desirable and convenient means for consumers. The intestine plays an important role in immune system. We hypothesized that orally administered HA would be transferred to both blood and lymph. In this study, we investigated how orally administered HA was absorbed from the gastrointestinal tract and how much HA was incorporated. Four HA formulations, HA-2,000, 8,000, 50,000 and 300,000, were administered to rats, and concentrations of HA in blood and lymph were determined. In the HA-2,000 group, the HA plasma concentration increased after oral administration. The highest lymph concentration of HA was also obtained by administration of HA-2,000. The plasma and lymph concentrations slightly increased after oral administration in the HA-8,000 group. On the other hand, little absorption was found in the HA-50,000 and 300,000 groups. It is speculated that smaller molecules of HA are more easily absorbed. HA-2,000 was absorbed mainly through the portal vein and through the lymph in gastrointestinal absorption. This is the first report showing that HAs, large molecular weight and water-soluble molecules, after oral administration are transferred not only into blood but also into lymph.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Pharmacoepidemiology and drug safety 29 8 873 - 880 2020年08月 [査読有り][通常論文]
     
    PURPOSE: When prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) for chronic kidney disease (CKD), patients' pathology and concomitant medications should be considered. In our pharmaceutical experience, NSAIDs are often prescribed by departments that are different from those that diagnosed CKD. That is, NSAIDs may be prescribed for patients without the advice of the clinicians who diagnosed them. In this study, we aimed to elucidate how frequently such cases occur. METHODS: We used the large health insurance claims database constructed by JMDC Inc., Tokyo. We evaluated the proportions of CKD diagnosis and NSAID prescription by different clinical departments and institutions. RESULTS: A total of 224 014 out-patients were included in the analysis; they were divided into CKD (n = 1501) and non-CKD groups (n = 222 513). The internal medicine departments diagnosed CKD most frequently (74.8% of the patients) and surgical departments rarely diagnosed CKD. However, the proportion of prescribed NSAIDs was high in other departments, especially surgical departments. In the CKD group, 50.4% of the patients received CKD diagnosis and NSAID prescription from different clinical departments; 72.8% of the patients received a diagnosis and prescription from different medical institutions. CONCLUSION: Our study revealed that NSAIDs are often prescribed to patients with CKD from different clinicians than those who diagnosed them.
  • Tatsuhiko Sakamoto, Yoshitaka Saito, Masaki Kobayashi, Takehiro Yamada, Yoh Takekuma, Masato Nakai, Koji Ogawa, Ken Iseki, Mitsuru Sugawara
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 28 7 3251 - 3257 2020年07月 [査読有り][通常論文]
     
    PURPOSE: There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication to be used is still not established. This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE. METHODS: Patients with hepatocellular carcinoma who were treated with TACE with epirubicin were retrospectively evaluated. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group (AE group), which includes 51 patients prophylactically administered with palonosetron 0.75 mg and dexamethasone 9.9 mg intravenously before TACE on day 1 and dexamethasone 6.6 mg intravenously on days 2 and 3, and control group with 101 patients without antiemetic premedication. RESULTS: Complete response rate in the entire evaluation period was significantly higher in the AE group compared with that in the control group. In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group. CONCLUSIONS: Premedication of palonosetron and dexamethasone significantly prevents the incidence and reduces the severity of gastrointestinal symptoms especially in the acute phase. Further studies will be needed to determine the most recommended 5-HT3 antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen.
  • Hiroyuki Tanaka, Hiroaki Hiraga, Yoh Takekuma, Toru Harabayashi, Satoshi Nagamori, Masayuki Endo, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 43 5 762 - 766 2020年05月01日 [査読有り][通常論文]
     
    The currently approved dose of pazopanib (800 mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib Cmin, and other clinical factors, including albumin and α-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. Cmin for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n = 4), 400 (n = 34), 600 (n = 4), and 800 mg (n = 1). Most patients (65%) who received a 400 mg dose had an effective pazopanib concentration (≧20 µg/mL), whereas 35% of patients who received the 400 mg dose had ineffective concentrations (<20 µg/mL). Logistic regression analysis revealed that only the albumin level was significantly associated with effective pazopanib concentrations (odds ratio: 1.37, p = 0.0234). In conclusion, a dose of 400 mg had been effective and well tolerated in more than half of patients in this study. However, therapeutic drug monitoring is necessary during pazopanib therapy.
  • Masayoshi Kumai, Yosuke Maeda, Mototsugu Miura, Kenkichi Tsuruga, Takehiro Yamada, Yoh Takekuma, Mitsuru Sugawara
    Case Reports in Oncology 13 1 281 - 284 2020年03月24日 [査読有り][通常論文]
     
    We present a case in which serotonin syndrome developed immediately after the initiation of low-dose methadone following an increase in oxycodone dose and the initiation of duloxetine. The symptoms of serotonin syndrome were alleviated and later disappeared upon cessation of methadone alone. The case was a 47-year-old woman with a desmoid tumor. The administration of duloxetine (20 mg/day) was initiated while the patient took oxycodone sustained-release tablets (40 mg/day). The following day, excessive perspiration, chills, and tremors appeared after the initiation of 15 mg/day methadone. Discontinuation of methadone led to an alleviation of the symptoms which completely disappeared 3 days later. The results suggest that low-dose methadone can trigger serotonin syndrome as early as after the first dose. Thus, it is important to be aware of the risks and to immediately take action if symptoms appear.
  • Interaction Between Piperacillin/Tazobactam and Warfarin: a Single-Center Retrospective Single-Arm Cohort Study
    Shota Kadomura, Yoh Takekuma, Shungo Imai, Hitoshi Kashiwagi, Kotaro Kawamoto, Tatsuya Itoh, Mitsuru Sugawara
    BPB Reports 3 2 65 - 69 2020年03月 [査読有り][通常論文]
  • Maaya Sasaki, Tsuyoshi Aoyama, Mitsuru Sugawara, Yoh Takekuma
    Drug metabolism and pharmacokinetics 35 1 102 - 110 2020年02月 [査読有り][通常論文]
     
    Nilotinib has bioavailability (BA) of only about 25% or less. The purpose of this study was to evaluate the influence of gastrointestinal activity on the absorption of nilotinib. In order to change gastrointestinal activity, mosapride was used for enhancement and butylscopolamine was used for suppression. Experiments on oral administration of nilotinib using rats whose gastrointestinal activity was altered by mosapride or butylscopolamine were carried out. The results of oral administration of acetaminophen to rats with peristalsis movement changed showed that the effects of peristalsis and gastric emptying rate (GER) on drug absorption could be evaluated in this experimental system. Similarly, even with nilotinib, no change in Tmax was observed, but Cmax increased and decreased significantly. Due to the change in gastrointestinal activity, Cmax of nilotinib changed greatly. This showed that gastrointestinal activity affected the emulsifying action of bile and that the absorbability changed. As a result of examining the contribution to the emulsifying action, it was found that when the bile does not exist in the gastrointestinal tract, absorption of nilotinib did not change even when gastrointestinal motility was enhanced. Therefore, the results suggested that gastrointestinal activity influenced the emulsifying action of bile and the absorption of nilotinib was changed.
  • Yuki Sato, Sayaka Yokoyama, Yoshiaki Yamaki, Yuta Nishimura, Mami Miyashita, Shingo Maruyama, Yoh Takekuma, Mitsuru Sugawara
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 142 105144 - 105144 2020年01月15日 [査読有り][通常論文]
     
    Emulsions have often been prepared to improve absorption of lipophilic compounds that have poor solubility. Coenzyme Q10 (CoQ10) is a lipophilic compound that has been used as an anti-aging supplement. We focused on oleyl polyethyleneoxy acetic acid, an oxa acid derivative, to prepare emulsions of CoQ10 with the expectation of application to oral pharmaceutics. Oxa acids were purified and classified into four groups based on the average length of the ethylene oxide chain. The emulsion that were prepared using the four oxa acid groups were administered to rats and the plasma concentration profiles of CoQ10 were analyzed. The absorption of CoQ10 was improved in all emulsion groups compared with that in the powder group. The emulsion using oxa acid (n = 9.0) greatly increased the plasma concentration of CoQ10. Absorption was also improved by using emulsions containing larger percentage of oxa acids (6%, 15% and 23%) to compared with the same oxa acid (n = 9.0). The effects of oxa acids on cell viability were almost the same as those of conventional surfactants such as polyoxyethylene (20) sorbitan monooleate (Tween 80). The results showed that oxa acids are useful to prepare emulsions for oral administration and that the absorption of CoQ10 using oxa acids is significantly improved by using our formulations.
  • Yoshitaka Saito, Kazuki Uchiyama, Tatsuhiko Sakamoto, Kojiro Yamazaki, Kosei Kubota, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 43 12 1969 - 1974 2020年 [査読有り]
     
    We previously reported that successive pharmaceutical care by oncology pharmacy specialists contributes to quality outpatient chemotherapy. However, there are a few reports regarding such care during immune checkpoint inhibitors (ICIs) treatment, despite increasing patients being treated with ICIs and the profile of immune-related adverse events being quite different from that of the adverse effects of cytotoxic agents. We retrospectively evaluated the effectiveness of continuous pharmaceutical care in outpatient ICI treatment, focusing especially on the period of providing pharmaceutical recommendations. The adoption rate, efficacy, and period of pharmaceutical interventions, such as prescription questions and pharmaceutical recommendations, were evaluated. A total of 3597 ICI administrations (366 patients) were evaluated. We performed 2625 face-to-face medication counseling. A total of 282 prescription questions and 147 pharmaceutical recommendations were conducted. Approximately 70% of the questions were regarding ordering of laboratory examination, and 86.5% of these questions were adopted. Pharmaceutical recommendations were categorized into medication recommendations (81.1%), examination recommendations (10.8%), and recommendation of expert consultation (8.1%). The adoption rate of pharmaceutical recommendations was 96.0, and 70% of the medication recommendations attenuated the symptoms. Finally, the provision rate of pharmaceutical recommendations was significantly higher in the first 3 months after ICI treatment initiation. We found that pharmaceutical care contributes to an improved quality of outpatient ICI treatment, and face-to-face pharmaceutical counseling up to 3 months after ICI treatment initiation is the most important.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 43 10 1519 - 1525 2020年 [査読有り][通常論文]
     
    The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment. As colchicine is a substrate for CYP3A4 and P-glycoprotein (P-gp), drug-drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April 2014 to March 2017 were identified using the Japanese large health insurance claims database. As the primary endpoint, we evaluated the concomitant prescription proportions of strong CYP3A4 and/or P-gp inhibitors classified as "contraindications for co-administration" with colchicine in patients with renal or liver impairment. We defined these cases as "inappropriate colchicine prescriptions." Additionally, factors affecting inappropriate colchicine prescriptions were analyzed. Among the 3302 enrolled patients, 43 (1.30%) were inappropriately prescribed colchicine. Of these 43 patients, 11 had baseline renal and/or liver impairment. By multiple regression analysis, the primary diseases "gout" and "Behçet's disease" were extracted as independent factors for inappropriate colchicine prescriptions with odds ratios of 0.40 (95% confidence interval: 0.19-0.84) and 4.93 (95% confidence interval: 2.12-11.5), respectively. We found that approximately 1% of patients had important colchicine interactions. Particularly, Behçet's disease was a risk factor for inappropriate prescriptions, with approximately 25% of patients showing renal and/or liver impairment (classified as "contraindications for co-administration"). These findings may be useful for medical professionals who prescribe colchicine therapy.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Journal of pharmaceutical health care and sciences 6 1 18 - 18 2020年 [査読有り][通常論文]
     
    Background: Ward pharmacists are required for the active implementation of therapeutic drug monitoring (TDM). This epidemiological study verified whether Japanese ward pharmacists contribute to improving the TDM implementation proportions of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents using the large health insurance claims database. Methods: The patients who received intravenous anti-MRSA agents from April 2012 to March 2017 were enrolled. We defined ward pharmacy service as the "drug management and guidance fee" and/or "inpatient pharmaceutical services premium". In addition, implementation of TDM was identified by "the specific drug treatment management fee". We compared the proportions of TDM implementation for vancomycin (VCM), teicoplanin (TEIC), and arbekacin (ABK) in the ward and non-ward pharmacy service groups. To avoid confounding, the propensity score method was employed. Moreover, the clinical variables affecting TDM implementation in each anti-MRSA agent were analyzed by using a multiple logistic regression model. Results: The following number of patients were included in the study: VCM (n = 2138), TEIC (n = 596), and ABK (n = 142). After propensity score matching, the proportions of TDM implementation for VCM and TEIC were higher in the ward pharmacy service group than in the non-ward pharmacy service group (VCM: 69.2% vs 60.3%, TEIC: 51.4% vs 34.7%), while no significant difference was observed for ABK (21.2% vs 23.1%). As independent clinical variables affecting TDM implementation for VCM and TEIC, several clinical variables, including ward pharmacy services, were extracted. In contrast, no clinical variables were extracted for ABK. Conclusions: We found that the ward pharmacy service is associated with the active implementation of TDM for anti-MRSA agents, such as VCM and TEIC.
  • Shungo Imai, Yoh Takekuma, Hitoshi Kashiwagi, Takayuki Miyai, Masaki Kobayashi, Ken Iseki, Mitsuru Sugawara
    PloS one 15 7 e0236789  2020年 [査読有り][通常論文]
     
    Artificial neural networks are the main tools for data mining and were inspired by the human brain and nervous system. Studies have demonstrated their usefulness in medicine. However, no studies have used artificial neural networks for the prediction of adverse drug reactions. We aimed to validate the usefulness of artificial neural networks for the prediction of adverse drug reactions and focused on vancomycin -induced nephrotoxicity. For constructing an artificial neural network, a multilayer perceptron algorithm was employed. A 10-fold cross validation method was adopted for evaluating the resultant artificial neural network. In total, 1141 patients who received vancomycin at Hokkaido University Hospital from November 2011 to February 2019 were enrolled. Among these patients, 179 (15.7%) developed vancomycin -induced nephrotoxicity. The top three risk factors of vancomycin -induced nephrotoxicity which are relatively important in the artificial neural networks were average vancomycin trough concentration ≥ 13.0 mg/L and concomitant use of piperacillin-tazobactam and vasopressor drugs. The predictive accuracy of the artificial neural network was 86.3% and that of the multiple logistic regression model (conventional statistical method) was 85.1%. Moreover, area under the receiver operating characteristic curve (AUROC) of the artificial neural network was 0.83. In the 10-fold cross-validation, the accuracy obtained was 86.0% and AUROC was 0.82. The artificial neural network model predicting the vancomycin -induced nephrotoxicity showed good predictive performance. This appears to be the first report of the usefulness of artificial neural networks for an adverse drug reactions risk prediction model.
  • Shungo Imai, Yoh Takekuma, Takayuki Miyai, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 43 1 188 - 193 2020年 [査読有り][通常論文]
     
    This study aimed to construct an optimal algorithm for initial dose settings of vancomycin (VCM) using machine learning (ML) with decision tree (DT) analysis. Patients who were administered intravenous VCM and underwent therapeutic drug monitoring (TDM) at the Hokkaido University Hospital were enrolled. The study period was November 2011 to March 2019. In total, 654 patients were included in the study. Patients were divided into two groups, training (patients who received VCM from November 2011 to December 2017; n = 496) and testing (patients who received VCM from January 2018 to March 2019; n = 158) groups. For the training group, DT analysis of the classification and regression tree algorithm was performed to construct an algorithm (called DT algorithm) for the initial dose settings of VCM. For the testing group, the rates of attaining the VCM therapeutic range (trough value = 10-15 and 10-20 mg/L) with the DT algorithm and three conventional dose-setting methods were compared for model evaluation. The DT algorithm was constructed to be used for patients with estimated glomerular filtration rate ≥50 mL/min and body weight ≥40 kg. As a result, the recommended daily doses ranged from 20.0 to 58.1 mg/kg. In model evaluation, the DT algorithm obtained the highest rates of attaining the VCM therapeutic range compared to conventional dose-setting methods. Therefore, our DT algorithm can be applied to clinical practice. In addition, ML is useful for setting drug doses.
  • Tsuyoshi Aoyama, Yoshihiko Shibayama, Tatsuhiko Furukawa, Mitsuru Sugawara, Yoh Takekuma
    Biological & pharmaceutical bulletin 42 11 1805 - 1813 2019年11月01日 [査読有り][通常論文]
     
    Tyrosine kinase inhibitors (TKIs) are used as the first choice for chronic myeloid leukemia (CML) pharmacotherapeutics. Some patients taking these drugs showed good therapeutic reactivity despite the disappearance of drugs from blood. We investigated whether these drugs have sustained effects even after their disappearance and whether their effects depend on their amounts of intracellular accumulation. Cell proliferation after exposure of K562 cells or Multidrug resistance-1 (MDR-1)-transfected K562 cells was determined by a cell counting kit-8 assay. The intracellular accumulation amount of the drug showing a sustained cytostatic effect was measured by ultra high performance liquid chromatography mass spectrometry. Cell viability decreased in a culture time-dependent manner after washing out nilotinib and dasatinib. The sustained cytostatic effect of dasatinib, but not that of nilotinib, correlated with the intracellular accumulation level. In contrast, imatinib showed continuous a cytostatic effect after drug washout for long-term exposure but not after drug washout for short-term exposure. These results suggest that a good response in patients with a low serum concentration of imatinib, nilotinib or dasatinib may be due to the cytostatic effect of that drug continues even after its disappearance in plasma.
  • Comparison of predictive performance of drug dose settings using renal function estimation equations based on the Japanese population: a preliminary retrospective study using vancomycin dosing data.
    Shungo Imai, Soyoko Kaburaki, Takayuki Miyai, Hitoshi Kashiwagi, Mitsuru Sugawara, Yoh Takekuma
    BPB Reports 2 5 80 - 85 2019年10月 [査読有り][通常論文]
  • 濱野 宏美, 土井 正剛, 武隈 洋, 菅原 満, 一木 崇宏
    日本老年薬学会雑誌 2 2 27 - 34 (一社)日本老年薬学会 2019年09月 [査読有り][通常論文]
     
    症例は70歳代女性で、かかりつけ医が当該患者を引き継ぐ前、アルツハイマー型認知症(AD)の診断にてドネペジル5mg/日を服用していた。その後、ドネペジル5mg/日からガランタサミン(GAL)8mg/日へ変更された。数ヵ月後に無症候性脳梗塞を発症し、近隣脳外科の退院後、ニセルゴリン錠5mg、レボドパ・カルビドパ配合錠、リバスチグミンパッチ4.5mg/日が開始された。貼付開始後から皮膚炎を発症し、ステロイド外用薬を使用したが改善しなかった。皮膚炎のためやむを得ずGAL服用へ処方が変更され、会話にはならないが発語が増加し、右手でコップを掴めるようになった。しかし、強い嘔気をきたして近隣病院へ入院しGAL服用は中止されたが、クロピドグレルとレボドパ・カルビドパ配合錠服用は継続されていた。高齢者施設に再入居後にGAL 4mg/日服用を開始したところ、悪化していた覚醒レベルは徐々に回復し、寝床上のみでの生活から車椅子に座り、リビングで過ごせるようになった。
  • Shota Kadomura, Yoh Takekuma, Yuki Sato, Masato Sumi, Kotaro Kawamoto, Tatsuya Itoh, Mitsuru Sugawara
    Journal of pharmaceutical health care and sciences 5 13 - 13 2019年 [査読有り][通常論文]
     
    Background: Piperacillin/tazobactam (PIPC/TAZ) and cefepime (CFPM) are commonly used for the treatment of nosocomial and healthcare-associated infections. Recent reports have suggested that the incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin (VCM) and PIPC/TAZ is higher than that in patients treated with CFPM. However, there have been few reports on a comparison of the incidences of AKI in patients treated with PIPC/TAZ monotherapy and patients treated with CFPM. In this study, we investigated whether the incidence of AKI in patients treated with PIPC/TAZ is higher than that in patients treated with CFPM. Methods: This study was a single-center retrospective observational study. Patients who died during the therapeutic period, patients younger than 18 years of age, and patients undergoing hemodialysis were excluded. Primary outcomes were the incidence of AKI and the AKIN stages defined by the Acute Kidney Injury Network. Secondary outcomes were discontinuation and/or change of antibiotics and initiation of dialysis due to AKI. We also investigated the time to onset and the risk factors of AKI in this population. Results: There were 163 patients in the PIPC/TAZ group and 103 patients in the CFPM group. The incidence of AKI in patients treated with PIPC/TAZ (8.6%) was significantly higher than that in patients treated with CFPM (0.9%) (odds ratio (OR), 9.53; 95% confidence interval (CI), 1.41-408; p= 0.011). AKI severity was mostly stage 1 in both groups. There was no discontinuation and/or changes of antibiotics and there was no initiation of dialysis in either group. The onset of AKI in the PIPC/TAZ group (median period of 4 days) was earlier than that in the CFPM group. PIPC/TAZ was determined to be an independent risk factor of AKI in multivariate analysis (adjusted OR, 9.56; 95% CI, 1.21-75.3; p = 0.032). Conclusions: This study showed that the incidence of AKI in patients who received PIPC/TAZ was higher than that in patients who received CFPM. Furthermore, the onset of AKI was earlier in patients who received PIPC/TAZ than in patients who received CFPM. PIPC/TAZ was an independent risk factor of AKI in this study population.
  • Soyoko Kaburaki, Eri Yoshimura, Nozomi Kojima, Hidefumi Ueno, Mitsuru Sugawara, Yoh Takekuma
    Health science reports 1 10 e85  2018年10月 [査読有り][通常論文]
     
    Background and aim: The Cockcroft-Gault (C-G) equation for estimation of creatinine clearance (CCr) is still used in a clinical setting for drug dosage adjustment. Because differences between measured and estimated CCr values have been reported, particularly for Japanese elderly people, the aim of this study was to improve the accuracy of CCr estimation equations, such as C-G and Orita-Horio, by fitting to newly obtained data. Also, glomerular filtration rate (GFR) estimation equations, such as the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and the eGFR equation for Japanese people, were studied to compare with measured CCr. Method: Data from 313 subjects over the age of 40 years with laboratory data available were used for analysis in this study. Special attention was paid to elderly people, and approximately 70% of the subjects were over the age of 65 years. Results: The accuracy of estimation by the two conventional (C-G, Orita-Horio) CCr estimation equations was greatly improved by introducing adjusted body weight for which the degree of obesity is over 30% instead of measured body weight. By fitting the coefficients of the estimation equations to the present population, the mean error was reduced by almost half, particularly for people over the age of 75. Although all the values calculated by the GFR estimation equations were underestimated compared with measured CCr due to secretion, a coefficient of determination of above 0.65 was obtained for all GFR estimation equations. Conclusions: Improvement of the fitted CCr estimation equations suggests that reconstruction of renal function estimation equations is required, especially for old people. Further work is required to find optimal renal function (CCr and/or GFR) estimation equations for drug dosage adjustment.
  • Yuki Sato, Tatsuru Joumura, Shunsuke Nashimoto, Sayaka Yokoyama, Yoh Takekuma, Hideto Yoshida, Mitsuru Sugawara
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 127 171 - 176 2018年06月 [査読有り][通常論文]
     
    Lutein is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. Some studies including our previous study showed very low absorption of lutein after oral administration. These studies also suggested that the absorption route of lutein from the small intestine involves not only the blood but also the lymph. The aim of this study was to clarify the transfer of lutein into lymph and the tissue distribution after oral administration of a solid dispersion (SD) and a self-microemulsifying drug delivery system (SMEDDS) for improvement of the absorption. We used thoracic lymph-cannulated rats. It was shown that the plasma concentrations of lutein in the SD and SMEDDS groups were increased compared with that in the powder group. The absorption of lutein after oral administration of each formulation was clearly evaluated by its cumulative amount in lymph. Our data clearly showed that lutein is transferred into the lymph stream from the small intestine.
  • Masahiro Imamura, Yusuke Nakamura, Mitsuru Sugawara
    Geriatrics & gerontology international 18 3 505 - 507 2018年03月 [査読有り][通常論文]
  • 武隈 洋, 森 綾子, 小林 正紀, 山田 勇磨, 佐藤 夕紀, 鳴海 克哉, 古堅 彩子, 菅原 満
    薬学雑誌 138 12 1579 - 1586 (公社)日本薬学会 2018年 [査読有り][通常論文]
     
    病院・薬局実務実習を履修する前の薬学部内での事前実習において模擬患者を相手に行ったロールプレイと、実務実習後に同じシナリオで行ったロールプレイとをRIASによって比較し、コミュニケーション能力がどのように変化しているか検討した。対象は、本学薬学部薬学科の学生で、4年次の事前実習時と6年次の実務実習後に同じ服薬指導のシナリオでロールプレイを行った19名とした。検討の結果、学生は実務実習を経てコミュニケーションへの慣れや知識の増加により発話が流暢になったことが示唆された。また、4年次に比べて6年次には、「単純な相槌」(Back-channel responses)が減少し、「同意・理解」(Shows agreement or understanding)が増加していたことから、相手に対する理解の姿勢を表現できるようになったものと思われた。発話内容をみると、4年次に比べて6年次には「聞き取り」の割合が減少し、「相手への気持ちの寄り添い」や「助言」の割合が増加していた。
  • 田中 寛之, 平賀 博明, 武隈 洋, 橋下 浩紀, 三浪 圭太, 原林 透, 永森 聡, 遠藤 雅之, 菅原 満
    TDM研究 34 3 140 - 140 (一社)日本TDM学会 2017年09月 [査読有り][通常論文]
  • 小学校の授業を通して見えてきたことと今後の課題
    佐藤夕紀, 宮下元樹, 菅原満
    道学薬 13 37 - 40 2017年05月 [査読無し][招待有り]
  • Nashimoto S, Sato Y, Takekuma Y, Sugawara M
    Biopharmaceutics & drug disposition 38 4 280 - 289 2017年05月 [査読有り][通常論文]
     
    Tocopherol is used not only as an ethical drug but also as a supplement. In 2008, it was reported that α-tocopherol is partly transported via an intestinal cholesterol transporter, Niemann-Pick C1-Like 1 (NPC1L1). Ezetimibe, a selective inhibitor of NPC1L1, is administered for a long time to inhibit cholesterol absorption and there is a possibility that the absorption of α-tocopherol is also inhibited by ezetimibe. This study investigated the influence of ezetimibe on the absorption of α-tocopherol with single administration and long-term administration. An approach to avoid its undesirable consequence was also examined. α-Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of α-tocopherol and tissue concentrations were investigated. The plasma concentration of α-tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of α-tocopherol was prevented by an administration interval of 4 h. In a group of rats administered for 2 months with a 4 h interval, not only the plasma concentration but also the liver concentration was increased compared with those in a group with concurrent combination intake of α-tocopherol and ezetimibe. The absorption of α-tocopherol was inhibited by ezetimibe. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Attention should be paid to the use of ezetimibe and components of NPC1L1 substrates such as α-tocopherol. Copyright © 2016 John Wiley & Sons, Ltd.
  • 武隈 洋, 石坂 悠, 高地 里佳, 吉村 恵理, 小嶋 希望, 上野 英文, 平野 卓哉, 野田 敏宏, 熊井 惠美, 菅原 満
    薬局薬学 9 1 159 - 168 (一社)日本薬局学会 2017年04月 [査読有り][通常論文]
     
    耳鼻咽喉科領域のアレルギー性咳嗽患者への抗アレルギー薬の使用実態を調査した。対象は市中保険薬局で抗アレルギー薬を交付された外来患者(耳鼻咽喉科受診)および総合病院内科を受診し抗アレルギー薬が処方された患者とした。抗アレルギー薬およびその併用薬からアレルギー性咳嗽症状を有すると推察される患者を選択し、アレルギー性咳嗽患者の割合および抗アレルギー薬の処方頻度を調査した。患者を湿性咳嗽と乾性咳嗽に分類し、咳症状に関する主訴と服用薬から治療効果を評価した。その結果、両施設ともにLTRA(ロイコトリエン受容体拮抗薬)および第二世代抗ヒスタミン薬の使用頻度が高かった。市中保険薬局では両者の併用頻度が最も高く、内科では単剤使用の頻度が最も高かった。湿性咳嗽および乾性咳嗽ともに症状が改善した60〜70%の患者でLTRAが使用されていた。乾性咳嗽を有する患者の多くが2剤以上の抗アレルギー薬を必要とした。(著者抄録)
  • Kazutaka Aonuma, Tsuyoshi Shiga, Hirotsugu Atarashi, Kosuke Doki, Hirotoshi Echizen, Nobuhisa Hagiwara, Junichi Hasegawa, Hideharu Hayashi, Kenzo Hirao, Fukiko Ichida, Takanori Ikeda, Yorinobu Maeda, Naoki Matsumoto, Toshiyuki Sakaeda, Wataru Shimizu, Mitsuru Sugawara, Kyoichi Totsuka, Yoshimasa Tsuchishita, Kazuyuki Ueno, Eiichi Watanabe, Masayuki Hashiguchi, Sumio Hirata, Hidefumi Kasai, Yoshiaki Matsumoto, Akihiko Nogami, Yukio Sekiguchi, Tokuko Shinohara, Atsushi Sugiyama, Naokata Sumitomo, Atsushi Suzuki, Naohiko Takahashi, Eiji Yukawa, Masato Homma, Minoru Horie, Hiroshi Inoue, Hiroshi Ito, Takanori Miura, Tohru Ohe, Kimikazu Shinozaki, Kazuhiko Tanaka
    Circulation journal : official journal of the Japanese Circulation Society 81 4 581 - 612 2017年03月24日 [査読有り][通常論文]
  • Simple blood sample pre-treatment to remove DAMPA in ARCHITECT® for methotrexate
    Tanaka H, Sako M, Morioka Y, Motoshige H, Takekuma Y, Kawamoto H, Sugawara M, Hiraga H
    TDM研究 34 1 1 - 7 2017年03月 [査読有り][通常論文]
  • Yoh Takekuma, Haruka Ishizaka, Masato Sumi, Yuki Sato, Mitsuru Sugawara
    JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES 19 4 511 - 519 2016年 [査読有り][通常論文]
     
    PURPOSE. Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone (PVPP) as a disintegrant. The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. METHODS. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodipheny lmethane, 2-aminobiphenyl, 2-(p-tolyl) benzoic acid or 4.4'-biphenol as principal agents, cellulose, lactose hydrate, PVPP and magnesium stearate as additives, were made by direct compression. The model tables were wrapped in paraffin papers and stored for 2 weeks at 40 degrees C/75% relative humidity (RH). Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. RESULTS. Model tablets with a simple composition were able to reproduce a decreased dissolution rate after storage at 40 degrees C/75% RH. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. 2-Benzylaniline tablets showed a remarkably decreased dissolution rate and 2-aminobiphenyl and 2-(p-tolyl) benzoic acid tablets showed slightly decreased dissolution rates, though 4,4'-biphenol tablets did not show a decrease dissolution rate. CONCLUSIONS. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions.
  • Yuki Tazawa, Akio Shigematsu, Kumiko Kasashi, Junichi Sugita, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima, Ken Iseki, Mitsuru Sugawara, Yoh Takekuma
    Journal of pharmaceutical health care and sciences 2 18 - 18 2016年 [査読有り][通常論文]
     
    BACKGROUND: We investigated the pharmacokinetics of etoposide (ETP) to reduce the inter-individual variations of ETP concentrations in patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation. We also carried out an in vivo study using rats to verify the dose adjustment. METHODS: This study included 20 adult patients. ETP was administered intravenously at a dose of 15 mg/kg once daily for 2 days (total dose: 30 mg/kg) combined with standard conditioning of cyclophosphamide and total body irradiation. In an in vivo study using rats, ETP was administered intravenously at a dose of 15 mg/kg or an adjusted dose. The ETP plasma concentration was determined by using HPLC. The pharmacokinetic parameters were estimated by using a 1-compartment model. RESULTS: The peak concentration (Cmax) of ETP and the area under the plasma concentration-time curve (AUC) of ETP differed greatly among patients (range of Cmax, 51.8 - 116.5 μg/mL; range of AUC, 870 - 2015 μg · h/mL). A significant relationship was found between Cmax and AUC (R = 0.85, P < 0.05). Distribution volume (Vd) was suggested to be one of the factors of inter-individual variation in plasma concentration of ETP in patients (range of Vd, 0.13 - 0.27 L/kg), and correlated with Alb and body weight (R = 0.56, P < 0.05; R = 0.40, P < 0.05 respectively). We predicted Vd of rats by body weight of rats (with normal albumin levels and renal function), and the dose of ETP was adjusted using predicted Vd. In the dose adjustment group, the target plasma ETP concentration was achieved and the variation of plasma ETP concentration was decreased. CONCLUSION: The results suggested that inter-individual variation of plasma concentration of ETP could be reduced by predicting Vd. Prediction of Vd is effective for reducing individual variation of ETP concentration and might enable a good therapeutic effect to be achieved.
  • Yuto Takekawa, Yuki Sato, Yoshiaki Yamaki, Mei Imai, Kazuma Noto, Masato Sumi, Yoh Takekuma, Ken Iseki, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 39 3 301 - 7 2016年 [査読有り][通常論文]
     
    Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann-Pick C1-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1 µM) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol.
  • 武隈 洋, 高地 里佳, 石坂 悠, 佐藤 夕紀, 鷲見 正人, 菅原 満
    医療薬学 40 3 135 - 146 (一社)日本医療薬学会 2014年03月 [査読有り][通常論文]
     
    開封後のスタチン製剤の安定性に及ぼす光・温度・湿度の影響について検討した。安定性評価の対象とした薬剤は、ロスバスタチン製剤1銘柄2規格、シンバスタチン製剤4銘柄、プラバスタチン製剤4銘柄である。安定性評価の対象薬剤を、一包化した状態を想定してPTPシートから出し、薬包紙を用いて1錠ずつ包んだ。また、散光条件下のみセロポリ分包紙を用いて1錠ずつ分包した。ロスバスタチン製剤はPTPから開封しても室温散光条件下で1年間安定で、一包化調剤後でも患者が通常家庭内で保存する分には大きな問題は生じないことが示唆されたが、粉砕調剤時には遮光保存が必須条件であることが示された。シンバスタチン製剤は、6ヵ月間保存した場合、すべての条件下で安定であったのは1製剤のみであった。プラバスタチン製剤は、すべての製剤において室温遮光条件下で6ヵ月間安定であることが示されたが、散光条件下では一部の製剤に変色が確認された。
  • Yuki Tazawa, Ippei Usukubo, Kazuki Takada, Yoh Takekuma, Yoshihiro Shibayama, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 37 8 1323 - 9 2014年 [査読有り][通常論文]
     
    Combination chemotherapy is often used to treat cancer. Many studies have shown schedule-dependent effects between anticancer drugs. Our previous studies showed that K-562 cells pretreated with non-cytotoxic concentrations of 4-hydroperoxycyclophosphamide (4-HPC), which is a preactivated analog of cyclophosphamide (CY), enhanced the cytotoxicity of etoposide (VP-16). The appearance of cellular resistance to anticancer drugs is a major problem in cancer chemotherapy. P-Glycoprotein (P-gp) plays an important role in drug resistance, and VP-16 is a substrate for this efflux pump. In the present study, we demonstrated schedule-dependent cytotoxicity of VP-16 and CY in P-gp-overexpressed K-562/P-gp cells. Cytotoxicity of VP-16 was enhanced in K-562/P-gp cells that were pretreated with a non-cytotoxic concentration of 4-HPC compared to that of cells not treated with 4-HPC. 4-HPC arrested the cell cycle at S phase. Cells in S phase are most sensitive to VP-16. The results suggest that cell cycle arrest by 4-HPC pretreatment may be responsible for the enhanced cytotoxicity of VP-16. The findings in this study should lead to improvements in clinical combination chemotherapy.
  • Yuki Sato, Hanami Mutoh, Mika Suzuki, Yoh Takekuma, Ken Iseki, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 36 12 2012 - 7 2013年 [査読有り][通常論文]
     
    Coenzyme Q10 (CoQ10) is an essential component in the electron-transport systems of mitochondria and bacteria and is often used as a supplementary treatment for some diseases. We previously reported that the bioavailability of CoQ10 powder was less than 10%. In this study, we investigated various preparations to improve the intestinal absorption of CoQ10 with focus on the effect of emulsification. We prepared a suspension and some emulsions with four types of surfactants and investigated the plasma concentration profile after oral administration to rats. The absorption of CoQ10 was improved by an emulsion formulation although there was little absorption of CoQ10 when a suspension was administered. However, little CoQ10 was absorbed in the bile duct-ligated group even when the emulsion formulation was administered (about 50% of the control group). Bile and emulsion formulation are essential for absorption of CoQ10. When the preparations containing Tween20 (polysorbate (20) sorbitan monolaurate) and Tween80 (polyoxyethylene (20) sorbitan monooleate) were administered, plasma concentrations of CoQ10 were higher than those obtained with preparations containing Tween65 (polyoxyethylene (20) sorbitan tristearate) and Span20 (sorbitan monolaurate). Tween20 and Tween80 have higher hydrophile-lipophile balance (HLB) values than those Tween65 and Span20. Our study suggests that highly lipophilic compounds like CoQ10 would diffuse the unstirred water layer and would easily access the intestinal apical membrane by an emulsion containing a surfactant with a high HLB value. Attention must be given to CoQ10 supplementation for patients whose bile is not excreted to the intestine such as patients with cholestasis.
  • Yuki Sato, Yu Kondo, Masato Sumi, Yoh Takekuma, Mitsuru Sugawara
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 16 3 494 - 501 2013年 [査読有り][通常論文]
     
    PURPOSE: Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. It has received much attention recently due to its preventive effect on age-related macular degeneration, and it has been consumed as a supplement. However, little information about the pharmacokinetic properties of lutein is available. Detailed knowledge of pharmacokinetic properties of lutein is needed for the development of pharmaceutics. In this study, we focused on the macular accumulation of lutein and investigated the uptake mechanism into human retinal pigment epithelial cells. METHODS: ARPE-19 cells were used for the study on the accumulation mechanism of lutein. The concentration of lutein was determined using an HPLC system. Involvement of scavenger class B type 1 (SR-B1) in the accumulation of lutein in ARPE-19 cells was suggested from the results of an inhibition study using block lipid transport 1 (BLT-1), a selective inhibitor of SR-B1. To investigate the involvement of SR-B1 in more detail, small interfering RNA (siRNA) was transfected and the mRNA and protein expression levels of SR-B1 were assessed by quantitative real-time reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: We confirmed a sufficient siRNA knockdown effect in both mRNA and protein expression levels of SR-B1. We then found that lutein uptake was significantly decreased by siRNA knockdown of SR-B1. CONCLUSION: The uptake of lutein was significantly decreased by 40% compared with the control uptake level. This suggested that active transport of lutein into ARPE-19 cells is mainly via SR-B1, given the result that lutein uptake at 4ºC was about 40% less that that at 37ºC.
  • Kazuo Matsubara, Masaru Asari, Manabu Suno, Toshio Awaya, Mitsuru Sugawara, Tomohiro Omura, Joe Yamamoto, Chikatoshi Maseda, Yoshikazu Tasaki, Hiroshi Shiono, Keiko Shimizu
    Legal medicine (Tokyo, Japan) 14 4 191 - 6 2012年07月 [査読有り][通常論文]
     
    When the population parameters of drug pharmacokinetics in the human body system are known, the time-course of a certain drug in an individual can generally be estimated by pharmacokinetics. In the present two cases where methamphetamine abusers were suspected to have inflicted mortalities in traffic accidents, the time-elapse or duration immediately after methamphetamine injection to the time when the accidents occurred became points of contention. In each case, we estimated the time-course of blood methamphetamine after the self-administration in the suspects using a 2-compartment pharmacokinetic model with known pharmacokinetic parameters from the literatures. If the injected amount can be determined to a certain extent, it is easy to calculate the average time-elapse after injection by referring to reference values. However, there is considerable individual variability in the elimination rate based on genetic polymorphism and a considerably large error range in the estimated time-elapse results. To minimize estimation errors in such cases, we also analyzed genotype of CYP2D6, which influenced methamphetamine metabolism. Estimation based on two time-point blood samples would usefully benefit legal authorities in passing ruling sentences in cases involving similar personalities and circumstances as those involved in the present study.
  • Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Taichi Kimura, Gentaro Hirokata, Susumu Shibasaki, Daisuke Fukumori, Sanae Haga, Mitsuru Sugawara, Tomomi Suzuki, Masahiko Taniguchi, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michitaka Ozaki, Toshiya Kamiyama, Satoru Todo
    Transplant international : official journal of the European Society for Organ Transplantation 25 6 696 - 706 2012年06月 [査読有り][通常論文]
     
    Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca(2+) concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca(2+) overload during the preservation and the activation of Ca(2+) -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.
  • 高橋 夏子, 小林 正紀, 板垣 史郎, 平野 剛, 武隈 洋, 菅原 満, 井関 健
    薬学雑誌 132 6 777 - 783 (公社)日本薬学会 2012年06月 [査読有り][通常論文]
     
    ヒト肺癌由来株化細胞A549およびヒト乳癌由来株化細胞MCF-7を用い、作用発現が明確な4種の薬物(シスプラチン(CDDP)、カルボプラチン(CBDCA)、パクリタキセル(PTX)、ゲムシタビン(GEM))を使用し、より簡便な抗癌薬の効果の判定と、投与設計への寄与を目的とし、in vitroでの抗癌薬の分類について基礎的検討を行った。CDDP、CBDCAは濃度依存的に抗腫瘍効果を発現する薬物として分類されることが推測された。一方、PTX、GEMについては細胞生存曲線の低濃度側へのシフトおよびIC 50値の著しい低下がみられことから、時間依存的に抗腫瘍効果を発揮する薬物として、分類可能であることが示唆された。更にCDDP、CBDCAの濃度依存性をより確実なものとするため、IC 50値を基準として前後10倍の濃度を設定し、濃度依存性を評価した結果、薬物濃度に比例した細胞生存率の低下がみられたことから、CDDP、CBDCAは濃度依存的に抗腫瘍効果を発揮する傾向の強い薬物であることが判明した。また、納所依存性の検討においても、用いた2種の細胞間で各抗癌薬の効果発現の様式に同様な傾向がみられた。研究結果より、細胞生存曲線及びIC 50値の変化を指標とし、作用の異なる抗癌薬を濃度依存的薬物および時間依存的薬物に分類できる可能性が示唆された。
  • 小澤 光一郎, 菅原 満, 関根 祐子, 中嶋 幹郎
    薬学雑誌 132 3 345 - 350 (公社)日本薬学会 2012年03月 [査読有り][通常論文]
     
    The six-year pharmacy program started in April 2006 in Japan. In the new program, students in the fifth year of the pharmacy course undergo a long-term practice experience (pharmacy clerkship) in community pharmacy and hospital pharmacy settings as compulsory 20 course credits. The new pharmacy practice experience started in May 2010. A start of the new system was a chance as for beginning movement, thus we conducted the questionnaire survey for the following steps. The finding obtained from our questionnaires indicated that many universities had already planned to execute new approaches, such as an advanced practice at outpatient units, an with medical students, and so on.
  • 長田 貴之, 柴山 良彦, 熊井 正貴, 山田 武宏, 笠師 久美子, 倉本 倫之介, 洲崎 真吾, 赤澤 茂, 真栄田 浩行, 坂下 智博, 折舘 伸彦, 本間 明宏, 福田 諭, 菅原 満, 井関 健
    医療薬学 38 1 51 - 55 (一社)日本医療薬学会 2012年01月 [査読有り][通常論文]
     
    オピオイドによる難治性の嘔気とめまいに対してヒスタミンH1受容体拮抗薬とペロスピロンの併用が有効であった2例を経験した。症例1は50歳代女で、舌癌の診断で、舌半側切除+両頸部郭清後、術後放射線治療の方針となった。放射線照射部位である舌根周辺に疼痛の増悪を認め、硫酸モルヒネを開始した。しかし、めまいと嘔気が発現し摂食困難となったため、オピオイドローテーションの方針となった。塩酸ペロスピロン錠を処方を開始すると、嘔吐、嘔気は消失し、摂食も可能となった。めまいもほぼ消失した。症例2は30歳代女で、中咽頭癌の診断で、シスプラチン超選択的動注併用放射線治療の方針となった。舌根部に疼痛を訴え、塩酸オキシコドン水和物徐放錠で疼痛をコントロールした。舌根の疼痛が増悪し、塩酸モルヒネ液を開始したが、嘔吐したためオピオイドローテーションの方針となった。塩酸ペロスピロン錠に変更し、嘔吐、嘔気とめまいは消失した。
  • Yoh Takekuma, Keiji Yagisawa, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 35 2 151 - 63 2012年 [査読有り][通常論文]
     
    Carvedilol is administered orally as a racemic mixture of R(+)- and S(-)-enantiomers for treatment of angina pectoris, hypertension and chronic heart failure. We have reported that enzyme kinetic parameters for carvedilol glucuronidation by human liver microsomes (HLM) differed greatly depending on the substrate form, namely, racemic carvedilol and each enantiomer. These phenomena were thought to be caused by mutual inhibition between carvedilol enantiomers during racemate glucuronidation. The aim of this study was to clarify the mechanism of these phenomena in HLM and human intestinal microsomes (HIM) and its relevance to uridine 5'-diphosphate (UDP)-glucuronosyl transferase (UGT) 1A1, UGT2B4 and UGT2B7, which mainly metabolize carvedilol directly in phase II enzymes. HLM apparently preferred metabolizing (S)-carvedilol to (R)-carvedilol in the racemate, but true activities of HLM for both glucuronidation were approximately equal. By determination of the inhibitory effects of (S)-carvedilol on (R)-carvedilol glucuronidation and vice versa, it was shown that (R)-carvedilol glucuronidation was more easily inhibited than was (S)-carvedilol glucuronidation. UGT2B7 was responsible for (S)-carvedilol glucuronidation in HLM. Ratios of contribution to (R)-carvedilol glucuronidation were approximately equal among UGT1A1, UGT2B4 and UGT2B7. However, enzyme kinetic parameters were different between the two lots of HLM used in this study, depending on the contribution ratio of UGT2B4, in which (R)-glucuronidation was much more easily inhibited by (S)-carvedilol than was (S)-glucuronidation by (R)-carvedilol. Meanwhile, HIM preferred metabolizing (R)-carvedilol, and this tendency was not different between the kinds of substrate form.
  • Yuki Sato, Risa Suzuki, Masaki Kobayashi, Shirou Itagaki, Takeshi Hirano, Toshihiro Noda, Satoshi Mizuno, Mitsuru Sugawara, Ken Iseki
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 15 2 256 - 64 2012年 [査読有り][通常論文]
     
    PURPOSE: Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesize lutein de novo, it must be digested as food. The physiological importance of an orally administered compound depends on its interaction with target tissues. It is therefore important to clarify the absorption mechanism in the intestine. Cholesterol membrane transporters Niemann-Pick C1 Like 1 (NPC1L1) and scavenger receptor class B type 1 (SR-B1) are involved in the intestinal absorption of highly lipophilic compounds including cholesterol. Ezetimibe, a selective inhibitor of intestinal NPC1L1, is the widespread lipid-lowering agent. It is important to investigate the possibility of food-drug interactions in order to prevent undesirable and harmful clinical consequences. The aim of this work was to determine whether NPC1L1, SR-B1 and other transporters are involved in absorption of lutein. METHODS: Caco-2 cells were used for accumulation and permeability study of lutein. Lutein concentration was determined by an HPLC system. The cDNA of transporters was isolated from total RNA of Caco-2 cells, and the expression of these transporters was confirmed by RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: Ezetimibe inhibited up to 40% of lutein accumulation by Caco-2 cell monolayers. Block lipid transport 1 (BLT-1), a selective chemical inhibitor of SR-B1, also inhibited lutein accumulation by Caco-2 cells. On the other hand, ATP-depletion reagents (sodium fluoride and sodium azide or carbonyl cyanide m-chlorophenylhydrazone) did not influence the accumulation or permeation of lutein significantly. CONCLUSIONS: The results show that lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters.
  • Yuki Tazawa, Kazunori Matsumura, Yoh Takekuma, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 35 7 1132 - 6 2012年 [査読有り][通常論文]
     
    In allogeneic bone marrow transplantation (allo-BMT) in patients with leukemia, the combination of VP-16 and cyclophosphamide (CY) is commonly used for the conditioning regimen. In the present study, we demonstrated schedule-dependent cytotoxicity of VP-16 and CY in K-562 cells. K-562 cells were pretreated with low concentrations (2.5 and 5 µg/mL) of 4-hydroperoxycyclophosphamide (40487S), which is a preactivated analog of CY. It was confirmed that these concentrations did not influence cell viability. Cells subsequently exposed to 0.5-100 µg/mL of VP-16 showed reduced the viability compared to that of control cells not treated with 40487S. In contrast, there was no change in the viability of K-562 cells pretreated with low concentrations (0.5 and 1 µg/mL) of VP-16. It was confirmed that these concentrations did not influence cell viability. Viability of subsequently exposed to 1-20 µg/mL was not different from that of control cells not treated with VP-16. VP-16 caused cell cycle arrest at G₂/M phase. On the other hand, 40487S arrested the cell cycle at S phase. Thymidine-synchronized cells, VP-16 showed cell cycle specificity for cell killing from early-S to mid-S phase. On the other hand, 40487S showed cell cycle-independent cytotoxicity. Exposure of cells to VP-16 after 40487S induced a greater cytotoxic effect on K-562 cells. The findings may lead to improvements in clinical combination chemotherapy.
  • Yuki Sato, Masaki Kobayashi, Shirou Itagaki, Takeshi Hirano, Toshihiro Noda, Satoshi Mizuno, Mitsuru Sugawara, Ken Iseki
    Food chemistry 127 3 893 - 8 2011年08月01日 [査読有り][通常論文]
     
    Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. Since humans cannot synthesise lutein de novo, it must be digested as food. The physiological importance of an orally administered compound depends on its interaction with target tissues. There is little information about the effects of intake of lutein in tissues other than the eyes. The aim of this study was to clarify the protective effect of lutein against oxidative injury using ischemia-reperfusion (I/R) model rats and to determine the relationship between pharmacokinetics and antioxidant activity of lutein. Intestinal I/R was induced by 30-min occlusion of the superior mesenteric artery followed by 60-min reperfusion. After 60min of reperfusion, intestinal tissue was used for analysis of Evans blue dye extravasation, lipid peroxidation and myeloperoxidase activity. Lutein administered before I/R had a significant protective effect against oxidative injury.
  • Yuki Sato, Masaki Kobayashi, Shirou Itagaki, Takeshi Hirano, Toshihiro Noda, Satoshi Mizuno, Mitsuru Sugawara, Ken Iseki
    Biopharmaceutics & drug disposition 32 3 151 - 8 2011年04月 [査読有り][通常論文]
     
    Lutein is a carotenoid found mainly in green leafy vegetables and is located in the macula lutea in the human eye. An intake of lutein as food is needed since humans cannot synthesize it de novo. Although lutein has received much attention recently due to its antioxidant activities, little information about the pharmacokinetic properties of lutein is available. Lutein emulsion formulation was used and the pharmacokinetics of lutein emulsion after oral administration to rats was investigated. The bioavailability of lutein using this formulation was calculated to be 5.20%. It was found that a large amount of lutein was accumulated in the intestinal mucosa. The absorption of orally administered compounds in the intestine can be enhanced by interaction with food or food components. Thus, the effect of food intake on the intestinal absorption of lutein was investigated. The plasma concentration of lutein after oral administration of the emulsion formulation was improved significantly by food intake. It is possible that the absorption of lutein in the intestine is improved significantly by some food components. Bile acids may also play important roles in the intestinal absorption of lutein since the absorption of lipophilic compounds such as cholesterol is related to bile acids. The results of these studies should contribute to an improvement of lutein absorption and provide important information for obtaining more effective pharmacological effects of lutein.
  • Yuki Sato, Shirou Itagaki, Toshimitsu Kurokawa, Jiro Ogura, Masaki Kobayashi, Takeshi Hirano, Mitsuru Sugawara, Ken Iseki
    International journal of pharmaceutics 403 1-2 136 - 8 2011年01月17日 [査読有り][通常論文]
     
    Dietary polyphenols are thought to be beneficial for human health as antioxidants. Coffee beans contain a common polyphenol, chlorogenic acid. Chlorogenic acid is the ester of caffeic acid and quinic acid. Although these polyphenols have received much attention, there is little evidence indicating a relationship between the effect and the rate of absorption. In this study, we focused on the beneficial effects of chlorogenic acid and caffeic acid, a major metabolite of chlorogenic acid. We carried out in vitro and in vivo experiments. In the in vitro study, caffeic acid had stronger antioxidant activity than that of chlorogenic acid. The uptake of chlorogenic acid by Caco-2 cells was much less than that of caffeic acid. The physiological importance of an orally administered compound depends on its availability for intestinal absorption and subsequent interaction with target tissues. We then used an intestinal ischemia-reperfusion model to evaluate antioxidant activities in vivo. We found that both chlorogenic acid and caffeic acid had effects on intestinal ischemia-reperfusion injury. Since caffeic acid has a stronger antioxidant activity than that of chlorogenic acid and chlorogenic acid is hydrolyzed into caffeic acid in the intestine, it is possible that caffeic acid plays a major role in the protective effect of chlorogenic acid against ischemia-reperfusion injury.
  • Yoshihiko Shibayama, Kou Nakano, Hiroshi Maeda, Miyuki Taguchi, Ryuji Ikeda, Mitsuru Sugawara, Ken Iseki, Yasuo Takeda, Katsushi Yamada
    Biological & pharmaceutical bulletin 34 3 433 - 5 2011年 [査読有り][通常論文]
     
    Sorafenib and sunitinib is a small molecule inhibitor of certain receptor tyrosine kinases, and have improved outcomes for patients with advanced renal cell carcinoma. Inhibitory concentration of 50% cell growth of sorafenib significantly rose to 6.4-fold in a multidrug resistance protein 2 (MRP2) transfected cell line versus control cell line. The concentration of sorafenib was significantly decreased to 74% of control cells after 3 h treatment. In contrast, a tyrosine kinase inhibitor sunitinib did not show alteration of inhibitory concentration of 50% cell growth and accumulation into the cells of MRP2 transfected cells. The present study suggest that sorafenib is a substrate for MRP2, suggesting that MRP2 may implicate drug resistance to sorafenib.
  • Yoshihiko Shibayama, Yoshitaka Iwashita, Yoshimi Yoshikawa, Tomoko Kondo, Ryuji Ikeda, Yasuo Takeda, Takayuki Osada, Mitsuru Sugawara, Katsushi Yamada, Ken Iseki
    Biological & pharmaceutical bulletin 34 9 1418 - 25 2011年 [査読有り][通常論文]
     
    5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for the treatment of cancers, and a common dose-limiting toxicity is neutropenia and diarrhea. In this study, we investigated the effect of 5-FU treatment on expression levels of drug transporters for SN-38 transportation and SN-38 absorption from the intestine following 5-FU treatment. Expression levels of several drug transporters and nuclear receptors in rats after 5-FU treatment were evaluated. SN-38 absorption from the intestine was evaluated by SN-38 concentration levels in serum following SN-38 injection into the intestine of 5-FU treated rats. The levels of renal multidrug resistance protein 2 (Mrp2) on day 4 after treatment (400 mg/kg) showed significant upregulation, 359.2 ± 33.2% (mean ± S.E.) of control. Mrp2 levels in the intestine were downregulated to 26.2 ± 8.4% of control. 5-FU treatment (400 mg/kg) also significantly downregurated expression levels of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) to 41.2 ± 14.7%, 15.7 ± 4.3% of control, respectively. To evaluate SN-38 absorption from the intestine, SN-38 was loaded in to the intestine on day 4 after 5-FU treatment. Pretreatment with 5-FU significantly increased SN-38 concentration in the blood 30, 60 and 90 min after SN-38 administration. The area under the curve for SN-38 in the 5-FU group was significantly higher than in vehicle groups. 5-FU treatment decreased expression levels of P-glycoprotein and Bcrp in intestine. The present study suggests that combination chemotherapy of 5-FU with irinotecan (CPT-11) may elevate SN-38 absorption from intestine.
  • Yuki Sato, Shirou Itagaki, Setsu Oikawa, Jiro Ogura, Masaki Kobayashi, Takeshi Hirano, Mitsuru Sugawara, Ken Iseki
    Biological & pharmaceutical bulletin 34 9 1448 - 54 2011年 [査読有り][通常論文]
     
    Ischemia-reperfusion (I/R) injury of the intestine is an important factor associated with high rates of morbidity and mortality. Intestinal I/R is a common clinical problem in the settings of severe burns, circulatory shock and strangulation ileus. Intestinal I/R damages remote organs and promotes multi-organ failure. It has been shown that enteral feeding before ischemic insults is beneficial for reducing organ injury and improving survival after intestinal I/R. In that study, the authors used a standard complex enteral diet and they suggested that it is important to find new nutrient formulas. Since reactive oxygen species are responsible for intestinal I/R injury, we focused on a dietary polyphenol, the soy isoflavone genistein. Genistein has a wide spectrum of biochemical and pharmacological activities. However, the possibility of a protective effect of genistein as enteral nutrition on I/R injury has not been investigated. We therefore investigated the protective effect of genistein on oxidative injury using intestinal I/R model rats. We found that genistein, which has combined antioxidant activity from radical scavenging, xanthine oxidase inhibition and chain-breaking effects, exhibits a protective effect on intestinal I/R injury. The results suggest that genistein, a soy isoflavone, has the possibility as a new nutrient formula of enteral feeding.
  • Miki Komatsu, Masahiko Takahata, Mitsuru Sugawara, Yoh Takekuma, Takashi Kato, Manabu Ito, Yuichiro Abe, Tohru Irie, Norimasa Iwasaki, Akio Minami
    European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 19 12 2149 - 55 2010年12月 [査読有り][通常論文]
     
    Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA) infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection. The penetration efficacy of linezolid into the annulus fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was lower than that of vancomycin (27, 11, and 14%, respectively). The penetration efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%, respectively), however, was higher than that of vancomycin (67 and 9%, respectively). These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection.
  • 板垣 史郎, 中田 千絵, 平野 剛, 鷹野 瑠美, 笠師 久美子, 菅原 満, 高橋 夏子, 小林 正紀, 井関 健
    医療薬学 36 9 696 - 702 (一社)日本医療薬学会 2010年09月 [査読有り][通常論文]
     
    放射線台療に伴う口腔粘膜障害に対する予防・軽減効果が期待される物質を探索した。16Gyの放射線照射を行った後、5日間培養したHO-1-N-1細胞を用いて、種々の化合物の障害抑制効果について検討した。抗酸化作用を有するN-アセチルシステイン(NAC)およびカテキン類に着目し、その障害抑制効果について検討した。高濃度のNACの添加により、放射線照射による細胞生存率の低下が有意に抑制された。カテキン類の添加により、放射線照射による細胞生存率の低下は有意に抑制された。NACおよびカテキン類の添加により、放射線照射による蛍光強度の増大は抑制された。HO-1-N-1細胞に放射線を照射したところ、アポトーシスに特徴的なDNAの断片化が観察され、アポトーシスが誘導されていることが示された。一方、NACおよびカテキン類の添加により、DNAの断片化は顕著に抑制された。
  • Shirou Itagaki, Akiko Ochiai, Masaki Kobayashi, Mitsuru Sugawara, Takeshi Hirano, Ken Iseki
    FOOD CHEMISTRY 120 2 552 - 555 2010年05月 [査読有り][通常論文]
     
    Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement. However, CoQ10 is taken up from the intestine into the circulation at a low rate. The absorption of compounds from the gastrointestinal tract is one of the important determinants for oral bioavailability. Secretory transport limits the Oral bioavailability of compounds. It has been reported that efflux transport of CoQ10 is mediated by P-glycoprotein (P-gp) in Caco-2 cells. We tried to improve intestinal absorption of CoQ10 by modulating P-gp. Since grapefruit juice (GFJ) is reported to inhibit P-gp function, we investigated the effect of GFJ on the transport of CoQ10 by Caco-2 cells. In the presence of GFJ, the basal-to-apical transport of CoQ10 was decreased and the uptake of CoQ10 was increased. These findings suggest that the combined administration of CoQ10 and GFJ could enhance CoQ10 absorption. (C) 2009 Elsevier Ltd. All rights reserved.
  • 斎藤 由起子, 平野 剛, 沖 洋充, 笠師 久美子, 菅原 満, 小林 正紀, 高橋 夏子, 板垣 史郎, 井関 健
    医療薬学 36 4 220 - 226 (一社)日本医療薬学会 2010年04月 [査読有り][通常論文]
     
    In vitro実験系による肺がん化学療法レジメンの抗腫瘍効果について検討した。肺がんのモデルとしてヒト肺扁平上皮がん由来A549細胞を使用した。CDDP+CPT-11(IP)療法において、CDDPは長期間にわたって抗腫瘍効果を示すことが示唆された。SN-38はday2からday5にかけて細胞生存率の回復を認め、CPT-11の1回日の投与により死滅したがん細胞が回復してきたところを再投与によりさらに攻撃するというレジメンの投与スケジュールに相関した。CDDP+VP-16(EP)療法において、各々の単剤のときと比較して抗腫瘍効果が増大することが示された。
  • Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Mitsuru Sugawara, Susumu Shibasaki, Gentaro Hirokata, Masaaki Zaitsu, Yusuke Tsunetoshhi, Michitaka Ozaki, Satoru Todo
    AMERICAN JOURNAL OF TRANSPLANTATION 10 494 - 494 2010年04月 [査読有り][通常論文]
  • 久保田 康生, 木村 俊也, 渡邉 紀子, 大崎 明美, 鈴木 克治, 菅原 満, 小山 司, 井関 健
    日本病院薬剤師会雑誌 46 3 359 - 362 (一社)日本病院薬剤師会 2010年03月 [査読有り][通常論文]
     
    気分障害圏の患者において薬物治療は症状・機能回復、再発予防のため重要であるが、拒薬に至る患者は4割といわれている。今回、患者に対し薬物療法への認識や考え方についてアンケート調査を行った結果、41%の患者にて拒薬の経験が認められた。理由として、副作用を避けるためなど認識の低さが原因であった。薬剤師が伝えた情報と患者の理解に差がみられる場合もある。そこで、患者の認知や思考の特性を知ることは服薬指導を充実させる方法として重要と考え、認知や思考を含め広く心理機能を測定できるロールシャッハテストに着目した。ロールシャッハテストは7つのクラスターを基に解釈される心理検査であるが、そのなかから認知や思考に関与するZd、X-%、HVIの3種の指標を選択した。HVI陽性において、拒薬との相関性が認められた。HVI陰性においてもZd、X-%が期待値外の場合、治療薬の理解に影響を与える可能性が考えられた。(著者抄録)
  • Takashi Yamamoto, Mitsuru Sugawara, Takashi Kikukawa, Seiji Miyauchi, Masahiro Yamaguchi, Atsushi Tero, Seiji Takagi, Toshiyuki Nakagaki
    Biophysical chemistry 147 1-2 59 - 65 2010年03月 [査読有り][通常論文]
     
    Transport across the cell membrane is crucial in drug delivery. However, the process is complicated because nucleoside derivatives that are commonly used as anti-viral drugs are transported through two different types of specific transporters: concentrative transporters and equilibrative transporters. Cross-disciplinary approaches involving both biological experiments and theoretical considerations are therefore necessary to study the transport of nucleoside analogues such as ribavirin. Here we constructed an experimental model system using the Xenopus laevis oocyte that expressed examples of both types of transporters: human concentrative nucleoside transporter 3 and human equilibrative transporter 1. We also performed a kinetic study. Experimental results showed that the transport of ribavirin could be reduced by inhibiting one of the two types of transporters, which seems to be counterintuitive. We therefore designed a simple mathematical model of the dynamics of ribavirin uptake and analyzed the model behaviors using a numerical simulation. The theoretical results reproduced the experimentally observed phenomena and suggested a possible mechanism for the process. Based on this mechanism, we predicted some potential methods for the effective uptake of ribavirin from a dynamics point of view.
  • 山崎 浩二郎, 武隈 洋, 西村 あや子, 宮本 剛典, 菅原 満, 井関 健
    TDM研究 26 4 137 - 141 (一社)日本TDM学会 2009年10月 [査読有り][通常論文]
     
    オキサゾリジノン系合成抗菌薬リネゾリド(LZD)は、2006年4月にMRSAに対する適応が追加された。LZDは腎機能低下例においても用法・用量の調節の必要がないと考えられており、血中濃度の測定もほとんど実施されていないのが現状である。今回、高度腎機能障害患者にLZDを投与した症例を経験し、その血中濃度を測定することによりLZDの体内動態への腎機能および透析の影響を検討したので報告する。MRSAによる菌血症の症例では、LZD投与中に腎機能が悪化し透析導入となった。そこで、透析時および非透析時の血中濃度を測定したところ、非透析時のLZDの排泄は健常人と比較して4倍程度遅延し、透析による除去率は50%程度であった。植皮部にMRSA感染がみられた症例では、透析は導入されていないが高度腎機能障害を有していた。LZD投与開始時より血中濃度を測定し、排泄への影響を確認し、その後の投与設計を行った。LZDの排泄は健常人と比較して2倍程度遅延しており、1回600mg1日2回の投与を1日1回へ減量した。その後の経過は良好であった。本検討により、少なくも高度腎機能障害患者においてはLZDの排泄遅延が起こり、LZDの血中濃度が非常に高く推移する可能性があることが明らかとなった。高度腎機能障害患者、透析患者においては血中濃度を測定することが非常に重要であり、今後のLZDの適正使用に貢献できるものと考えられる。(著者抄録)
  • 鷹野 瑠美, 平野 剛, 中田 千絵, 笠師 久美子, 菅原 満, 小林 正紀, 板垣 史郎, 井関 健
    医療薬学 35 4 247 - 253 (一社)日本医療薬学会 2009年04月 [査読有り][通常論文]
     
    癌化学療法に伴う口内炎の予防・改善に有効な抗酸化物質を探索するため、種々の化合物についてスーパーオキシドアニオン消去作用を評価した。対象物は含嗽として汎用されている3薬剤、抗酸化作用が記載されている8薬剤、カテキンのEGCgを用いた。その結果、含嗽剤ではアロプリノールの消去作用がレバミピドと比較して非常に強く、カモスタットはほとんど消去作用を示さなかった。他剤ではトラニラスト、メサラジン、ピロキシカムは作用が強く、ガベキサート、L-カルボシステインは弱かった。また、EGCgはアロプリノールと同等の強い消去作用を示した。次いで、組織障害に関与するラジカル連鎖反応停止作用を調べた結果、含嗽3薬剤には同作用は認めず、メサラジン、EGCgには強力な作用を認めた。更に、酸化障害性口内炎モデルに対する細胞障害抑制作用を調べたところ、EGCgは強力な効果を、アロプリノール、メサラジンは弱い効果を示し、レバミピド、カモスタットには効果を認めなかった。
  • 久保田 康生, 小林 正紀, 笠師 久美子, 高畑 むつみ, 菅原 満, 橋野 聡, 井関 健
    医療薬学 35 3 213 - 218 (一社)日本医療薬学会 2009年03月 [査読有り][通常論文]
     
    57歳女。多発性骨髄腫を発症した。MP(メルファラン+プレドニゾロン)療法を開始し、ビスホスホネート製剤を併用したが、病勢のコントロールが不良であった。サリドマイド+デキサメタゾン療法を開始したが奏効しなかった。自己末梢血幹細胞移植は、十分なCD34陽性細胞数を得ることができず施行できなかった。サリドマイド併用によるCP(シクロホスファミド+プレドニゾロン)療法、サリドマイド併用による少量のシクロホスファミドの内服治療を順次施行したが、出血性膀胱炎などの副作用により継続できなかった。非血縁者間同種造血幹細胞移植を施行し、GVHD予防としてFK506の持続点滴を開始した。内視鏡検査と病理検査により回盲部と結腸における急性消化管GVHDの発症を確認した。プロピオン酸ベクロメタゾン(BDP)腸溶性カプセル剤を投与し、改善傾向を認めた。
  • Hitoshi Kashiwagi, Kojiro Yamazaki, Yoh Takekuma, Vadivel Ganapathy, Mitsuru Sugawara
    Amino acids 36 2 219 - 30 2009年02月 [査読有り][通常論文]
     
    Several studies have demonstrated that the activity of system A is upregulated by insulin, osmotic shock and amino acid deprivation. However, the mechanisms are not clear. We carried out studies using L6 rat skeletal muscle cells to clarify the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation. The upregulation was found to be due to an increase in Vmax, not Km. Chloroquine and wortmannin inhibited the upregulation induced by insulin stimulation and amino acid deprivation but not that induced by osmotic shock. On the other hand, cycloheximide and actinomycin D inhibited the upregulation by each stimulation. Moreover, PD98059 and SP600125 inhibited only amino acid deprivation-induced upregulation and SB202190 inhibited only insulin-induced upregulation. Our findings indicate that the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation are different in L6 cells. Western blot and RT-PCR analysis showed an increase in system A at the protein and mRNA levels with each stimulation.
  • Improvement of renal function estimation equations for elderly Japanese people
    Kaburaki, S, Yoshimura, E, Kojima, N, Ueno, H, Sugawara, M, Takekuma, Y
    Health Science Reports 2008年09月 [査読有り][通常論文]
  • Shirou Itagaki, Akiko Ochiai, Masaki Kobayashi, Mitsuru Sugawara, Takeshi Hirano, Ken Iseki
    Journal of agricultural and food chemistry 56 16 6923 - 7 2008年08月27日 [査読有り][通常論文]
     
    In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.
  • 菅原 満, 山澤 裕司, 齋藤 嘉津彦, 小林 道也, 田中 寛之, 唯野 貢司
    TDM研究 25 1 28 - 36 (一社)日本TDM学会 2008年01月 [査読有り][通常論文]
     
    MRSA感染症治療を目的にTDM施行下にTEICが投与された症例の前向き調査を2005年12月から2007年3月の期間、北海道TDM研究会に所属する17施設で実施した。調査に先立ち、TEICの基本投与法は添付文書に記載されている用法用量、初日800mgの負荷投与、2日目以降は400mgの維持用量投与とし、目標トラフ濃度は10μg/mLに設定した。調査票が回収された102例について、TEICの適正な投与法および目標トラフ濃度10μg/mLの妥当性について検討を行った。その結果、TDM実施によりほぼ全例が最終的には10μg/mLの目標トラフ濃度にコントロールされたが、その到達時期はさまざまであった。臨床所見(体温、CRP、白血球数)はTEIC投与前後で有意な改善を認め、細菌学的有効率は75.9%だった。投与早期に目標トラフ濃度を確保しそれを維持した症例群は、それ以外の症例群に比べて細菌学的効果が優れていた。投与開始3日間に基本投与法より多い投与量が使用された症例群は全例が目標トラフに到達したが、基本投与法の症例群では約半数例が目標トラフ濃度に到達しなかった。TEICの添付文書に記載されている用法用量、初日400mg、2日目以降200mgの維持用量投与をした症例群では全例が目標トラフ濃度に到達しなかった。TEICの投与早期の血中濃度と肝・腎機能の検査値との関係を調べたところ、相関性は認められなかった。今回の検討では、TEICはTDMを施行し投与早期からトラフ濃度を10μg/mL上に確保、維持することが効果的な使用法であると考えられ、そのための投与法を再検討する必要があると思われた。(著者抄録)
  • 清川 真美, 澤口 利香, 須田 範行, 武隈 洋, 菅原 満, 相馬 孝光, 川嶋 望, 筒井 裕之, 井関 健
    医療薬学 34 1 20 - 25 (一社)日本医療薬学会 2008年01月 [査読有り][通常論文]
     
    造影剤投与を受けた患者に発現する造影剤腎症に対するN-アセチルシステイン(NAC)の予防効果を検討した。また、従来のNAC液の不快な臭いと味覚を改善したNACゼリー製剤の服用性を評価した。腎症予防効果の対象はNACを服用した造影剤投与患者(NAC群)67名と、それ以前に検査を受けたNAC非服用造影剤投与患者(対照群)81名で、腎障害の有無を血清クレアチニン値で評価した。NACゼリー製剤の服用感はNAC群の35名を対象としてアンケート調査を行った。その結果、NAC群の腎障害は対照群に比べて有意に低く、NACは腎機能低下を予防することが示唆された。また、種々の合併症を持つ患者の造影剤腎症に起因する腎機能悪化を予防する可能性が示された。一方、NACゼリー製剤はNAC液の不快な臭いや味覚を改善するが、その味付けには改善の余地があると思われた。
  • Shirou Itagaki, Makoto Chiba, Masaki Kobayashi, Mitsuru Sugawara, Michiya Kobayashi, Takeshi Hirano, Ken Iseki
    Biochimica et biophysica acta 1778 1 270 - 5 2008年01月 [査読有り][通常論文]
     
    It has been reported that the transport function for organic anions on the kidney is maintained in multidrug resistance-associated protein 2 (Mrp2)-deficient rats. Different from Mrp2-deficient rats, Long-Evans Cinnamon (LEC) rats have impaired urinary excretion of Mrp2-substrate, phenolsulfonphthalein (PSP). PSP is transported by the potential-sensitive urate transport system in rat brush-border membranes. We analyzed the function of PSP transport system in LEC rats. Unlike Long-Evans Agouti (LEA) rats, the initial uptake of PSP and urate into the renal brush-border membrane vesicles of LEC rats were not significantly enhanced in the presence of positive intravesicular potential, suggesting that the potential-sensitive urate transport system is impaired in LEC rats. LEC rats should be useful for elucidating the potential-sensitive urate transport system in rats at the molecular level.
  • Shirou Itagaki, Makoto Chiba, Masaki Kobayashi, Mitsuru Sugawara, Michlya Kobayashi, Takeshi Hirano, Ken Iseki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1778 1 270 - 275 2008年01月 [査読有り][通常論文]
     
    It has been reported that the transport function for organic anions on the kidney is maintained in multidrug resistance-associated protein 2 (Mrp2)-deficient rats. Different from Mrp2-deficient rats, Long-Evans Cinnamon (LEC) rats have impaired urinary excretion of Mrp2-substrate, phenolsulfonphthalein (PSP). PSP is transported by the potential-sensitive urate transport system in Tat brush-border membranes. We analyzed the function of PSP transport system in LEC rats. Unlike Long-Evans Agouti (LEA) rats, the initial uptake of PSP and urate into the renal brush-border membrane vesicles of LEC rats were not significantly enhanced in the presence of positive intravesicular potential, suggesting that the potential-sensitive urate transport system is impaired in LEC rats. LEC rats should be useful for elucidating the potential-sensitive urate transport system in rats at the molecular level. (c) 2007 Elsevier B.V. All rights reserved.
  • Yoh Takekuma, Toru Takenaka, Koujiro Yamazaki, Kazuyuki Ueno, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 30 11 2146 - 53 2007年11月 [査読有り][通常論文]
     
    Carvedilol, an alpha- and beta-adrenergic blocking drug, is mainly metabolized by CYP2D6, UGT1A1, UGT2B4 and UGT2B7. This drug is administered orally as a racemic mixture of R(+)- and S(-)-enantiomers. It has been reported that CYP2D6 prefers metabolizing S-carvedilol to R-carvedilol stereoselectively. On the other hand, stereoselective metabolism of carvedilol by UGTs is still unclear. Moreover, we have reported that patients with chronic heart failure who had polymorphism in CYP2D6, UGT1A1 and/or UGT2B7 had lower metabolic activity and oral clearance than did patients with no polymorphism. The aim of this study was to clarify stereoselective metabolism of carvedilol by UGT1A1 and UGT2B7 and to determine by using a recombinant enzyme-introduced mutation whether genetic mutation in UGT1A1 and UGT2B7 causes reduction in metabolic activity for carvedilol. A glucuronidation assay using human liver microsomes and recombinant UGT1A1 and UGT2B7 expressed in HeLa cells demonstrated that UGT1A1 prefers metabolizing R-carvedilol to S-carvedilol. On the other hand, UGT2B7 prefers metabolizing S-carvedilol to R-carvedilol. Moreover, G71R mutation of UGT1A1 reduced both affinity and capacity but did not affect stereoselective metabolism. On the other hand, both A71S and H268Y mutations of UGT2B7 reduced capacity but did not affect affinity and, as a result, the efficiency of metabolism was remarkably reduced. However, as in the case of UGT1A1, neither of the mutations affected stereoselective metabolism.
  • Yoh Takekuma, Toru Takenaka, Masami Kiyokawa, Koujiro Yamazaki, Hiroshi Okamoto, Akira Kitabatake, Hiroyuki Tsutsui, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 30 3 537 - 42 2007年03月 [査読有り][通常論文]
     
    In our previous study it was observed that the frequencies of UGT1A1*6, UGT2B7*3 and CYP2D6*10 in patients who have a low level ability of glucuronidation were significantly higher than those in patients with a high level of ability of glucuronidation. The same tendency was found in the frequency of CYP2D6*5, though there was no significant difference. The purpose of this study was to evaluate the effects of the polymorphism on pharmacokinetics of carvedilol by population pharmacokinetic analysis. Population pharmacokinetic analysis was performed using 373 plasma concentrations from 41 patients with chronic heart failure or angina pectoris. A one compartment pharmacokinetic model with first-order absorption (for oral dosing) was used to describe the concentration-versus-time data for carvedilol. We examined the effects of various clinical and genetic covariables in the regression models for clearance and volume of distribution. The results suggested that the factors of interindividual variation for carvedilol clearance were creatinine clearance and polymorphisms of UGT2B7 and CYP2D6 in the Japanese population with heart disease. It was estimated that UGT2B7*3 decreased the clearance of carvedilol by 37%, but UGT2B7*2 did not show any effect. Clearance in the patients who have intermediate activity of CYP2D6 was decreased by 39%.
  • Takashi Yamamoto, Kenichi Kuniki, Yoh Takekuma, Takeshi Hirano, Ken Iseki, Mitsuru Sugawara
    European journal of pharmacology 557 1 1 - 8 2007年02月14日 [査読有り][通常論文]
     
    We investigated the mechanism of the transport of ribavirin (1-beta-D-ribofuranosyl-1,2,4-trizole-3-carboxamide) into placental epithelial cells using human choriocarcinoma (BeWo) cells and Xenopus oocytes expressing human nucleoside transporters. In BeWo cells, when a relatively low concentration (123 nM) of ribavirin was used, both Na(+)-dependent uptake and -independent uptake of ribavirin were observed. On the other hand, when a higher concentration (100 microM) of ribavirin was used, Na(+)-independent uptake was observed, but there was only a slight Na(+)-dependent uptake. In Xenopus oocytes, influxes of ribavirin mediated by hCNT2 (concentrative nucleoside transporter 2), hCNT3 (concentrative nucleoside transporter 3), hENT1 (equilibrative nucleoside transporter 1) and hENT2 (equilibrative nucleoside transporter 2) were saturable, and apparent K(m) values were 18.0 microM, 14.2 microM, 3.46 mM and 3.71 mM, respectively. These data indicate that hCNT2 and hCNT3 have higher affinity for ribavirin than do hENT1 and hENT2. Moreover, analysis by RT-PCR showed that BeWo cells express mRNA of hCNT3, hENT1 and hENT2. These results suggest that ribavirin is taken up by BeWo cells via both the high-affinity Na(+)-dependent transporter hCNT3 and the low-affinity Na(+)-independent transporters hENT1 and hENT2.
  • 久保田 康生, 中里 恭子, 須田 範行, 沖 洋充, 菅原 満, 小林 道也, 齊藤 浩司, 井関 健
    医療薬学 33 2 152 - 158 (一社)日本医療薬学会 2007年02月 [査読有り][通常論文]
     
    患者の入院中の各種状況を把握し、それに応じたテーラーメイド的な服薬指導を行うため、病棟担当薬剤師からセンター担当薬剤師向けへの患者情報伝達手段の方法・内容の検討とその評価を行った。外来治療センターで抗がん剤調製業務および服薬指導を担当しているセンター担当薬剤師5例を対象とし、選択・記述併用形式のアンケート調査を行った。センター担当薬剤師が必要としている情報のアンケート調査結果を基に、病棟担当薬剤師から提供可能な情報を抽出し、外来治療センターへの連絡表を作成した。外来治療センターでの治療患者のおよそ30%の患者に対し、連絡表を使用しており、その有用性が見出されてきている。
  • Yoh Takekuma, Haruka Kakiuchi, Koujiro Yamazaki, Seiji Miyauchi, Takashi Kikukawa, Naoki Kamo, Vadivel Ganapathy, Mitsuru Sugawara
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 10 1 71 - 85 2007年 [査読有り][通常論文]
     
    PURPOSE: Mycophenolic acid (MPA), an immunosuppressant, is excreted as its glucuronized form, MPAG. In humans, MPAG is mostly excreted into urine, whereas more than 80% of the dose is excreted into bile in rats. The aim of this study was to clarify the cause of the species difference. We investigated whether MPAG is a substrate of human organic anion transporters (hOATs), and we compared the affinities of multi-drug resistance-associated protein 2 (MRP2) for MPAG in rats and humans. METHODS: The inhibitory effects of MPAG on the uptake of typical substrates via hOAT1 and hOAT3 were determined using HeLa cells heterologously expressing hOAT1 and Xenopus laevis oocytes heterologously expressing hOAT3. MPAG transport activity via hOAT1 and hOAT3 was determined by the two-microelectrode voltage-clamp technique using Xenopus laevis oocytes expressing hOAT1 and hOAT3. The affinities of MPAG for hMRP2 and rMrp2 were determined by the inhibitory effects of MPAG on p-aminohippuric acid (a typical substrate) uptake using membrane vesicles expressing hMRP2 or rMrp2. RESULTS: MPAG inhibited the uptake of PAH via hOAT1 and hOAT3, and calculated IC50 values were 222.6+/-26.6 microM and 41.5+/-11.5 microM, respectively. However, MPAG was not transported by hOAT1 and hOAT3. MPAG strongly inhibited the uptake of PAH via both rMrp2 and hMRP2. However, the magnitudes of inhibitory effects were different. The calculated IC50 values were 286.2+/-157.3 microM and 1036.8+/-330.5 microM, respectively. CONCLUSION: MPAG is not a substrate but is an inhibitor of hOAT1 and hOAT3. The affinity of rMRP2 to MPAG was about 3.6 times as high as that of hMRP2. Therefore, the difference of affinity between hMRP2 and rMrp2 is a possible mechanism of the difference of excretion ratio of MPAG between rats and human.
  • 山崎 浩二郎, 武隈 洋, 志賀 弘康, 菅原 満, 小澤 剛久, 柴田 万里子, 橋本 聡一, 森本 裕二
    TDM研究 23 4 253 - 256 (一社)日本TDM学会 2006年10月 [査読有り][通常論文]
     
    酢酸フレカイニド(FLC)は、Vaughan Williams分類のI c群に属する抗不整脈薬である。近年、抗不整脈薬は鎮痛補助薬としても有効であることが示され、特に神経因性疼痛(ニューロパシックペイン)に対して鎮痛効果があるとされている。そこで著者らは、神経因性疼痛に対するFLCのドラッグチャレンジテストを設計し、その鎮痛効果とFLCの血中濃度との関係について検討した。対象は、帯状疱疹後神経痛、複雑型局部疼痛症候群、難治性神経因性疼痛などの診断を受け、既存の治療法で疼痛軽減が得られなかった、または効果が頭打ちになり罹患より3ヵ月以上経過した症例とした。5名中4名においてVisual analog scale(VAS)の低下が認められた。また、その5名において、FLCの血中濃度に大きな個体差は認められず、投与終了5分後で200〜400ng/mL、30分後で140〜180ng/mL、120分後で100ng/mL付近で推移した。この血中濃度推移とVASの推移の関係より、FLCの神経因性疼痛に対する最低有効血中濃度は140〜180ng/mL付近であることが示唆された。(著者抄録)
  • 久保田 康生, 沖 洋充, 山崎 浩一, 菅原 満, 西村 正治, 井関 健
    日本病院薬剤師会雑誌 42 7 927 - 929 (一社)日本病院薬剤師会 2006年07月 [査読有り][通常論文]
     
    入院患者を73例を対象として,健康食品に関する認識や摂取状況を調査し,特に,化学療法施行患者への服薬指導における健康食品摂取に対する薬剤師としての対応を検証した.また,これらの調査から得られた情報を基に,健康食品に関するデータベースの構築を行った.57.5%が健康食品を摂取し,特にがん患者の摂取率が高かった.摂取群,非摂取群ともに健康被害や相互作用の可能性を疑う頻度に差は見られなかった.既知の健康被害や相互作用だけでも回避できるよう,摂取状況は医療従事者へ報告してもらうよう促すため「患者用注意書き」を作成した.医療従事者へ可能な限りの正確な情報をいち早く提供できるようデータベースを構築した
  • Yoh Takekuma, Toru Takenaka, Masami Kiyokawa, Koujiro Yamazaki, Hiroshi Okamoto, Akira Kitabatake, Hiroyuki Tsutsui, Mitsuru Sugawara
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 9 1 101 - 12 2006年 [査読有り][通常論文]
     
    PURPOSE: It has been reported that carvedilol, which has beta-adrenergic blocking and vasodilating activities, is mainly metabolized by UDP-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B7 and CYP2D6. The aim of this study was to determine whether the activity of glucuronidation has an influence on the area under the curve (AUC) of carvedilol and whether polymorphisms in UGTs and CYP2D6 contribute to individual variation in disposition of carvedilol in Japanese. METHODS: Plasma concentrations of carvedilol and its glucuronide were determined by reversed-phase high-performance liquid chromatography (HPLC). Genotyping of UGT1A1, UGT2B4 and UGT2B7 genes was carried out by the direct sequence method. CYP2D6 genotyping was carried out using an amplification refractory mutation system (ARMS) assay and PCR-restriction fragment length polymorphism (RFLP). RESULTS: The level of carvedilol glucuronidation ability in the high-level AUC group was significantly lower than that in the low-level group. The frequencies of UGT1A1*6, UGT2B7*3 and CYP2D6*10 in the low level ability of glucuronidation group were significantly higher than those in the high level group, and the same tendency was found in the frequency of CYP2D6*5, though there was no significant difference. CONCLUSION: Polymorphisms of UGT1A1, UGT2B7 and CYP2D6 strongly affect the pharmacokinetics and disposition of carvedilol in Japanese.
  • 笠師 久美子, 須田 範行, 鄭 漢忠, 菅原 満, 井関 健
    日本医療薬学会年会講演要旨集 16 0 435 - 435 一般社団法人 日本医療薬学会 2006年 [査読有り][通常論文]
  • 志賀 弘康, 川合 真次, 荻野 修, 菅原 満, 遠藤 晃, 櫻井 恒太郎, 宮崎 勝巳
    医療薬学 31 12 1027 - 1035 (一社)日本医療薬学会 2005年12月 [査読有り][通常論文]
     
    より正確に,かつ効率的に麻薬を管理することを目的として,麻薬オーダリングシステム(麻薬オーダ)を構築した.各種オーダ(処方,注射,物流)と連動させることにより,麻薬帳票類の自動作成を可能とした麻薬オーダの詳細と,その運用方法,さらにはその有用性を検討した.オーダの麻薬データを利用し,各種麻薬の入出庫データ,廃棄データ等をあらためて手入力することなく,麻薬帳票・届け出類の自動作成が可能となった.これにより麻薬使用量等の集計業務は簡便になり,各種帳票類の作成に要する時間も大幅に短縮し,麻薬受払簿の正確性の向上で,システム導入前と比較して在庫確認作業も簡便になった
  • 瀬戸 恵介, 須田 範行, 荻野 修, 菅原 満
    日本病院薬剤師会雑誌 41 11 1407 - 1409 (一社)日本病院薬剤師会 2005年11月 [査読有り][通常論文]
     
    外来治療センターを利用している患者49名を対象に,がん化学療法の現状と問題点についてアンケート調査を行った.その結果,約70%の患者が薬についての注意事項や副作用についてのパンフレットを希望していた.また,多くの患者が薬の名前や副作用を知っているのに対し,その対処法や治療後に注意すべき点を知っているのは約1/3と少なかった.現在,このアンケート結果を基に患者向け情報提供用紙を作成し,外来治療センターを初めて利用した患者にこの情報提供用紙を用い,患者個別に注射剤や副作用の説明を行っている
  • Mitsuru Sugawara, Shota Kadomura, Xin He, Yoh Takekuma, Naonori Kohri, Katsumi Miyazaki
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 26 1 1 - 8 2005年09月 [査読有り][通常論文]
     
    The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system. This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method. Elution profiles and predicted absorption of these preparations in gastric pH conditions similar to those in healthy subjects and patients with achlorhydria were compared with those of a physical mixture and commercial tablets. When a physical mixture or commercial tablets were used, the elution profile and predicted absorption of both albendazole and dipyridamole were extremely pH-dependent. On the other hand, when a solid dispersion and granules were used, elution and predicted absorption were not affected by changes in pH of the flowing solution in a drug-dissolving vessel. These results are in agreement with the results of our previous in vivo study using gastric acidity-controlled rabbits. Our results suggest that this in vitro system is useful for the evaluation of oral absorption of pH-independent controlled-release preparations.
  • Shirou Itagaki, Soji Shimamoto, Mitsuru Sugawara, Michiya Kobayashi, Katsumi Miyazaki, Takeshi Hirano, Ken Iseki
    European journal of pharmacology 518 2-3 83 - 9 2005年08月22日 [査読有り][通常論文]
     
    The purpose of this study was to elucidate the transporter-mediated secretion systems for phenolsulfonphthalein in brush-border membranes. In human and rat renal brush-border membranes, a potential-sensitive transport system has been shown to be involved in the efflux of organic anions. The uptake of phenolsulfonphthalein into rat renal brush-border membrane vesicles was stimulated by an inside-positive membrane potential. This potential-sensitive uptake of phenolsulfonphthalein was inhibited by probenecid, pyrazinoate and urate. p-Aminohippurate had no effect on the potential-sensitive uptake of phenolsulfonphthalein. Moreover, urate competitively inhibited the uptake of phenolsulfonphthalein. On the other hand, the uptake of phenolsulfonphthalein was slightly increased in the presence of an outward Cl- gradient. These results suggest that phenolsulfonphthalein has high affinity for the potential-sensitive urate transport system but has low affinity for an anion exchanger.
  • Mitsuru Sugawara, Takahiro Mochizuki, Yoh Takekuma, Katsumi Miyazaki
    Biochimica et biophysica acta 1714 2 85 - 92 2005年08月15日 [査読有り][通常論文]
     
    It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogenous compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1. The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl derivative>7-methyl derivative>3-methyl derivative falling dotsxanthine>1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid>1,3-dimethyluric acid>1,7-dimethyluric acid>1-methyluric acid>uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds.
  • M Sugawara, T Mochizuki, Y Takekuma, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1714 2 85 - 92 2005年08月 [査読有り][通常論文]
     
    It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogetious compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1 Inhibitory effects of xanthine-and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1 The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl defivative > 7-methyl derivative > 3-methyl derivative(.)=(.) xanthine > 1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid > 1,3-dimethyluric acid > 1,7-dimethyluric acid > 1-methyluric acid > uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds. (c) 2005 Elsevier B.V All rights reserved.
  • 武隈 洋, 岩井 美和子, 藤原 俊恵, 川岸 亨, 熊井 正貴, 松浦 麻耶, 馬渕 朋美, 須田 範行, 宮本 剛典, 荻野 修, 菅原 満, 宮崎 勝巳
    医療薬学 31 7 575 - 584 (一社)日本医療薬学会 2005年07月 [査読有り][通常論文]
     
    がん化学療法における調剤および処方鑑査を知識や経験年数の差によらず,正確かつ円滑に行うために,全診療科のがん化学療法プロトコールを収集し,そのデータベースを構築・運用した.構築したデータベースの使用マニュアルを作成した.疾患を12に分類し,必要な情報をプロトコール名,対象診療科,対象疾患,薬品名,投与量,単位,投与日,投与経路の項目に沿って,表形式に整理・電子データ化した.データベースシステムは独自の特化したものではなく,他の施設でも内容のメンテナンスを行えば利用可能な汎用データベースシステムとしたため,多くの施設へ提供が可能となり,情報発信基地としての大学病院の役割を果たし得たと考えた
  • 須田 範行, 新里 利香, 清川 真美, 金内 美妃, 菅原 満, 郡 修徳, 宮崎 勝巳
    医療薬学 31 5 355 - 359 (一社)日本医療薬学会 2005年05月 [査読有り][通常論文]
     
    患者のコンプライアンスの向上を目的として内用液に代わる剤形としてゲル化剤を用いたゼリー製剤の調製を試みた.アセチルシステイン(AC)は市販の内用液剤,ゲル化剤はゼラチンあるいは寒天を用いた.矯味剤にはアミノレバンEN専用フレーバーミックスを用いた.ゲル化剤にはゼラチンが適切であった.3種の矯味剤のうち被験者50%がリンゴ味を選択した.ミルクコーヒー味,抹茶味を選択した者はおのおの25%であった.AC水と比較し,ACジュース,ACゼリーは評価が高かった.すべての項目でゼラチンゼリーの評価は最も高く,特に,においの項目では被験者の90%が最もよいと答えた.ACゼリーの服用感はAC内用液と比較し著しく優れていることが示唆された.ゼラチンゼリーは第1液,第2液ともに試験開始後約10分で100%の溶出率を示した.少なくとも7日間は品質を保証できた
  • Shirou Itagaki, Makoto Chiba, Soji Shimamoto, Mitsuru Sugawara, Michiya Kobayashi, Katsumi Miyazaki, Takeshi Hirano, Ken Iseki
    Drug metabolism and pharmacokinetics 20 1 72 - 8 2005年02月 [査読有り][通常論文]
     
    It is known that secretory transport limits the oral bioavailability of certain drugs. However, there is little information on the secretion of anionic compounds in the intestine. Phenolsulfonphthalein (PSP) and p-aminohippuric acid (PAH) have been used widely as substrates for organic anion transport systems. PAH is transported in the secretory direction in the intestine. It is possible that PSP and PAH share the same transport system at the mucosal membrane. The purpose of this study was to characterize the transport system for PSP in the intestine. In the jejunum, the serosal-to-mucosal permeation rate of PSP was significantly reduced in an ATP-depleted condition, whereas a significant difference was not observed in the ileum. Some multidrug resistance-associated protein 2 (Mrp2) inhibitors inhibited PSP permeation in the jejunum. However, pravastatin, a substrate of Mrp2, did not inhibit the PSP permeation. The jejunal secretory transport of pravastatin was significantly reduced in an ATP-depleted condition and by addition of probenecid, but PSP did not affect the jejunal permeation of pravastatin. These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane.
  • Elangovan Gopal, You-Jun Fei, Mitsuru Sugawara, Seiji Miyauchi, Lina Zhuang, Pamela Martin, Sylvia B Smith, Puttur D Prasad, Vadivel Ganapathy
    The Journal of biological chemistry 279 43 44522 - 32 2004年10月22日 [査読有り][通常論文]
     
    We report here on the expression of slc5a8 in kidney and its relevance to Na(+)-coupled reabsorption of lactate. slc5a8 is the murine ortholog of SLC5A8, a candidate tumor suppressor gene, which we recently cloned from human intestine and demonstrated its functional identity as a Na(+)-coupled transporter for short-chain fatty acids and lactate. The slc5a8 cDNA, cloned from mouse kidney, codes for a protein consisting of 611 amino acids. When expressed heterologously in mammalian cells or Xenopus oocytes, slc5a8 mediates Na(+)-coupled electrogenic transport of lactate/pyruvate as well as short-chain fatty acids (e.g. acetate, propionate, and butyrate). The Na+/fatty acid stoichiometry varies depending on the fatty acid substrate (2:1 for lactate and 4:1 for propionate). This phenomenon of variable Na+/substrate stoichiometry depending on the fatty acid substrate is also demonstrable with human SLC5A8. In situ hybridization with sagittal sections of mouse kidney demonstrates abundant expression of the transcripts in the cortex as well as the medulla. Brush border membrane vesicles prepared from rabbit kidney are able to transport lactate in a Na(+)-coupled manner. The transport process exhibits the overshoot phenomenon, indicating uphill lactate transport in response to the transmembrane Na+ gradient. The Na(+)-coupled lactate transport in these membrane vesicles is inhibitable by short-chain fatty acids. We conclude that slc5a8 is expressed abundantly in the kidney and that it plays a role in the active reabsorption of lactate. slc5a8 is the first transporter known to be expressed in mammalian kidney that has the ability to mediate the Na(+)-coupled reabsorption of lactate.
  • Shirou Itagaki, Soji Shimamoto, Takeshi Hirano, Ken Iseki, Mitsuru Sugawara, Sachiho Nishimura, Michio Fujimoto, Michiya Kobayashi, Katsumi Miyazaki
    Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 7 2 227 - 34 2004年07月13日 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to determine the cause of the decline in phenolsulfonphthalein (PSP) excretion in Long-Evans Cinnamon (LEC) rats. METHODS: The uptake of PSP into rat renal basolateral membrane vesicles (BLMV) was studied. Cyclosporin A (CYA) was used to modulate an ATP-dependent primary active transporter. PSP was intravenously injected into rats with or without CYA. The transcellular transport of PSP was examined by using primary cultured renal proximal tubule cells (PTC). RESULTS: No significant difference was found between the uptake of PSP into renal BLMV of Wistar rats and that into renal BLMV of LEC rats. In the presence of CYA, the urinary excretion and the plasma concentrations of PSP in Wistar rats were decreased and increased, respectively. In primary cultured renal PTC from Wistar rats, the basal-to-apical transport of PSP was greater than that in the opposite direction and the basal-to-apical transport of PSP was substantially reduced by the addition of CYA. However, CYA did not affect the basal-to-apical transport of PSP in PTC from LEC rats. CONCLUSIONS: The results suggest that PSP is transported by primary active organic anion transporter and that the activity level of this transporter is reduced in LEC rats.
  • Xin He, Mitsuru Sugawara, Yoh Takekuma, Katsumi Miyazaki
    Antimicrobial agents and chemotherapy 48 7 2604 - 9 2004年07月 [査読有り][通常論文]
     
    The aim of this study was to elucidate the absorption mechanism in Caco-2 and rat intestine models in order to improve the accuracy of prediction of oral absorption of ester prodrugs. Pivampicillin and cefcapene pivoxil hydrochloride (CFPN-PI), ester-type oral antibiotics, were chosen as model ester prodrugs. The level of esterase activity in Caco-2 cells was lower than that measured in the rat jejunum when p-nitrophenyl acetate was used as a substrate. Almost complete ester hydrolysis occurred before the ester prodrugs reached the basolateral side of the monolayer, and the disappearance of prodrugs was thought to be due to metabolism or transport after addition to the apical side of the monolayer. When pivampicillin and CFPN-PI were used, the amounts of ampicillin and cefcapene (CFPN) produced by hydrolysis of prodrugs were increased because intracellular degradation of prodrugs resulted in intracellular accumulation. On the other hand, when ampicillin or CFPN was used, only a small amount of the drug reached the basolateral side of the monolayers and no intracellular accumulation was observed. The permeability of CFPN-PI, the solubility of which is dependent on the acidity of gastric juice, across a Caco-2 monolayer or rat intestine, was also investigated by using an in vitro system that mimics the physiological state of the human gastrointestinal tract. The oral absorption of CFPN-PI in humans is predicted to be good either in the Caco-2 model or in the rat intestine model. It is concluded that our system may be a valuable tool for evaluation of oral absorption of ester prodrugs metabolized during permeation through the intestinal epithelium. Broader evaluation of such a system is warranted.
  • Satoshi Kishino, Maki Ogawa, Yoh Takekuma, Mitsuru Sugawara, Tsuyoshi Shimamura, Hiroyuki Furukawa, Satoru Todo, Katsumi Miyazaki
    Clinical transplantation 18 2 124 - 9 2004年04月 [査読有り][通常論文]
     
    The urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) is considered to be the simplest and most practical method for estimation of hepatic cytochrome P450 3A4 (CYP3A4) activity as a non-invasive marker of human in vivo CYP3A4 activity. However, the inter- and intra-individual variability of the urinary 6beta-OHF/F ratio during liver regeneration and the effect of variability on optimal dose of tacrolimus have not yet been clarified. The objective of this study was to clarify the change in the urinary 6beta-OHF/F ratio during liver regeneration and to determine the effect of the liver graft function on the optimal tacrolimus dose in liver transplant recipients. Two liver transplant recipients (one male and one female) and eight healthy volunteers (five males and three females) were enrolled in this study. Urine samples were collected from the recipients from 08.00 hours for 24 h on post-transplant period, 1-10 and 21-30 days postoperatively. In the healthy volunteers, morning spot urine samples were collected at 08.00 hours. The mean urinary 6beta-OHF/F ratio in the immediate postoperative period was significantly low (p < 0.05). However, a marked difference in the regulation of CYP3A4 activity during liver regeneration was found in the two recipients. A significant correlation was found between the urinary 6beta-OHF/F ratio and the C/D ratio of tacrolimus (R = 0.658, p < 0.05). The urinary 6beta-OHF/F ratio is a useful probe for estimating the variability of CYP3A4 activity in liver transplant recipients in early postoperative phase. Future studies should evaluate the clinical usefulness of the urinary 6beta-OHF/F ratio as a predictor of tacrolimus pharmacokinetics in liver transplantation.
  • Shirou Itagaki, Mitsuru Sugawara, Michiya Kobayashi, Katsumi Miyazaki, Takeshi Hirano, Ken Iseki
    Drug metabolism and pharmacokinetics 19 2 150 - 4 2004年04月 [査読有り][通常論文]
     
    Long-Evans Cinnamon (LEC) rats have an abnormality similar to that observed in Wilson's disease in humans and are therefore a good animal model for the study of Wilson's disease. LEC rats develop hereditary hepatitis and severe jaundice. Mutant animals with hyperbilirubinemia have been widely used as animal models for human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats (EHBR) have defective biliary excretion of organic anions. Thus, biliary excretion of sulfobromophthalein (BSP) and urinary excretion of phenolsulfonphthalein (PSP) in LEC rats were compared with those in Long-Evans Agouti (LEA) rats. In LEC rats, the excretion of BSP, a multidrug resistance-associated protein 2 (Mrp2/Abcc2) substrate, was significantly decreased compared to that in LEA rats. It has been reported that the transport function for organic anions on the kidney is maintained in EHBR. However, the urinary excretion of PSP is impaired in LEC rats. It is possible that organic anion transporters responsible for the urinary excretion of PSP in LEA rats and EHBR are impaired in LEC rats. It is important to elucidate the relationship between organic anion secretion and Wilson's disease.
  • T. Nakagawa, S. Kishino, S. Itoh, M. Sugawara, K. Miyazaki
    British Journal of Clinical Pharmacology 57 2 226  2004年02月 [査読有り][通常論文]
  • 岸野 吏志, 馬渕 朋美, 武隈 洋, 菅原 満, 嶋村 剛, 古川 裕之, 藤堂 省, 宮崎 勝巳
    TDM研究 21 1 21 - 25 (一社)日本TDM学会 2004年01月 [査読有り][通常論文]
     
    38歳男性生体部分肝移植患者におけるリネゾリド(LZD)連続投与中の血中動態を検討した.LZDは,1回600mg(点滴時間2時間),1日2回連続投与とした.総(結合型+非結合型)薬物の最高血中濃度は31.70μg/ml,トラフ濃度は10.75±3.76μg/mlであり,非結合型薬物の最高血中濃度は25.29μg/ml,トラフ濃度は8.97±2.84μg/mlであった.また,消失半減期は7.46hr,分布容積は5.54L,Vssは30.63Lであり,健常人と異なる傾向が認められた.一方,総薬物,および非結合型薬物の血中濃度曲線面積は,それぞれ228.21μg/ml・hr,210.72μg/ml・hrと,健常人と比較して増加する傾向が認められた.また,肝移植患者の血漿蛋白結合率は13.18±4.67%であり,健常人の平均結合率に比べて顕著に低下していることが明らかになった.この症例では副作用が認められなかったことから,LZDは臓器移植患者においても比較的安全に使用可能であることが示唆された
  • Xin He, Shota Kadomura, Yoh Takekuma, Mitsuru Sugawara, Katsumi Miyazaki
    Journal of pharmaceutical sciences 93 1 71 - 7 2004年01月 [査読有り][通常論文]
     
    One purpose of this study was to develop a new system for the prediction of pH-dependent soluble drug absorption that takes into account the physiological condition of the gastrointestinal tract. Another purpose was to establish several models of different gastric acidities: a normal gastric acidity model, a low gastric acidity model (a model of achlorhydria), a temporarily elevated gastric acidity model (a model of a case in which an acidic drug was coadministered to temporarily elevate gastric acidity in the case of low gastric acidity), a weak antacid model (a model of a case in which a weak antacid drug, such as an H(2) receptor antagonist, was coadministered to temporarily elevate pH up to 6), and a strong antacid model (a model of a case in which a strong antacid drug, such as magnesium hydroxide, was coadministered to temporarily elevate pH up to 8.0). These models were used to evaluate variation in pH-related absorption in humans. Dipyridamole preparation (Persantin tablets) and glibenclamide preparation (Euglucon tablets), both poorly water-soluble and pH-dependent soluble drugs, were chosen as model drugs to determine whether absorption is altered by changes in levels of gastric acid. The extent of absorption of dipyridamole was remarkably lower when gastric pH was continuously elevated to 6.0, whereas it was increased when gastric pH temporarily decreased to 1.8. The extent of absorption of glibenclamide increased dramatically when gastric pH temporarily increased to 8.0, but did not change when gastric pH temporarily increased to 6.0. These results are consistent with reported results obtained in clinical studies. The results suggest that pH-related variations in absorption in humans can be accurately predicted using our new system.
  • T Nakagawa, S Kishino, S Itoh, M Sugawara, K Miyazaki
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 56 6 664 - 669 2003年12月 [査読有り][通常論文]
     
    Aims The F1S and A genetic variants of alpha(1)-acid glycoprotein (AAG) change under various physiological and pathological conditions. They also vary in their drug binding abilities. We have studied the stereoselective binding ability of each of the AAG variants using enantiomers of disopyramide (DP) and warfarin (WR). Methods The AAG variants were separated by hydroxyapatite chromatography. Binding of drug enantiomers to the AAG variants was studied by the Hummel-Dreyer method. The characteristics of the binding activities were examined by Scatchard plot analysis. The first five amino-terminal amino acids (residues 112-116) of the cyanogen bromide (CNBr) fragment (residues 112-181) of each of the separated AAG fractions were elucidated by Edman degradation. Results Commercial AAG was separated into two main fractions. Residues 112-116 of fraction 2 were identical to the amino acid sequences predicted from the AAG A gene, LAFDV, and encode the F1S variant. In fraction 3, the deduced amino acid sequence of the AAG B gene, FGSYL, was established, and encodes the A variant. The binding affinities of both DP enantiomers in fraction 3 were significantly higher than those in fraction 2. The differences between dissociation constants (Kd) in fractions 2 and 3 were 5.2-fold for (S)-DP (P < 0.05) and 3.7-fold for (R)-DP (P < 0.001). The dissociation constant of (S)-DP (0.39 +/- 0.08 muM) was lower than that of (R)-DP (0.53 +/- 0.10 muM) in fraction 3 [95% confidence interval (CI) - 0.282, - 0.010; P < 0.05], although the binding activities of the DP enantiomers were almost the same in fraction 2. By contrast WR enantiomers had a higher binding affinity in fraction 2 than in fraction 3, the differences in dissociation constants between fractions 2 and 3 being 12.6-fold for (S)-WR (P < 0.001) and 8.3-fold for (R)-WR (P < 0.001). The dissociation constant of (S)-WR (0.28 +/- 0.10 muM) was significantly lower than that of (R)-WR (0.48 +/- 0.08 muM) in fraction 2 (95% CI - 0.369, - 0.028; P < 0.05), but there were no significant differences between the binding activities of WR enantiomers in fraction 3. Conclusions DP and WR enantiomers bind preferentially to fraction 3 and fraction 2, respectively. Fractions 2 and 3 are encoded by the AAG A and the AAG B genes, respectively.
  • 須田 範行, 今野 安大, 森田 豊, 中田 宏, 菅原 満, 宮崎 正三, 宮崎 勝巳
    医療薬学 29 6 705 - 710 (一社)日本医療薬学会 2003年12月 [査読有り][通常論文]
     
    メシル酸カモスタット口腔内停留性を調整し,その物理的性質及び口腔内停留性について検討した.20名の健康成人被験者に対するアンケートから矯味としてミククコーヒー味を選択し,D-マンニトールを賦形剤としPVPを結合剤として錠剤を調整し,十分な硬度と口腔内崩壊性を持つことを確かめた.口腔内停留性実験の結果,この口腔内崩壊錠はメシル酸カモスタットの粘膜付着性及び口腔内停留性が含嗽剤よりも優れていることが明らかとなり,口に含むだけで唾液で速やかに崩壊し,水を用いなくても容易に服用でき,服薬コンプライアンスの向上が期待できる
  • S Kishino, Y Takekuma, M Sugawara, T Shimamura, H Furukawa, S Todo, K Miyazaki
    CLINICAL TRANSPLANTATION 17 5 412 - 416 2003年10月 [査読有り][通常論文]
     
    In adult-to-adult living donor liver transplantation (LDLT), the graft volume is inevitably much smaller than the ideal liver mass ( standard liver volume) for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver support. However, little is known about the influence of CVVHD on the elimination of tacrolimus. The objective of this study was to elucidate the effect of CVVHD on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size grafts. Three liver transplant recipients ( one male and two females) and donors ( two males and one female) were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD. Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no significant difference between concentrations of tacrolimus in blood sampled at inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD.
  • Xin He, Mitsuru Sugawara, Michiya Kobayashi, Yoh Takekuma, Katsumi Miyazaki
    International journal of pharmaceutics 263 1-2 35 - 44 2003年09月16日 [査読有り][通常論文]
     
    We developed an in vitro system simulating the physiological condition in the gastrointestinal (GI) tract for prediction of oral absorption of relatively water-soluble drugs and ester prodrug pivampicillin. This evaluation system includes a drug-dissolving vessel (DDV, assumed stomach), a pH adjustment vessel (PAV, assumed intestine) and a side-by-side diffusion chamber that is mounted by a Caco-2 monolayer, which is grown on a polycarbonate filter, or by a rat intestine between the donor and receiver compartments. Our proposed system can accommodate large amounts of solid drugs, simulating a drastic pH change process in GI tract, that is, an orally administered solid drug is dissolved in the stomach (pH 1-2) and transferred to the intestine (pH 6), and that dissolution process can also be monitored. The optimal flow rates for our system are 0.35-1.10 ml/min. Using this system, cumulative permeations of eight relatively water-soluble drugs were compared, and these cumulative permeations indicated the ability of drug absorption in humans. Drugs that permeated across a Caco-2 monolayer at cumulative permeation of more than 0.03% or over 0.04% in rat intestine can be almost completely absorbed in humans. If the cumulative permeation across a Caco-2 monolayer is lower than 0.03% or below 0.04% in the rat intestine, there was a good linear correlation between cumulative permeation across a Caco-2 monolayer and oral absorption in humans, or between cumulative permeation across a rat intestine and oral absorption in humans. In the case of relatively water-soluble drugs, a good linear correlation was obtained between cumulative permeation across a Caco-2 monolayer and cumulative permeation across a rat intestine. This result indicates that it is possible to predict the oral absorption of a relatively water-soluble drug in humans based on the cumulative permeation of the drug across a Caco-2 monolayer and/or a rat intestine. The time course of permeation of the ester prodrug pivampicillin, which is metabolized in a Caco-2 monolayer or in a rat intestine, was also evaluated. It stated clearly that it is also possible to predict the oral absorption of pivampicillin in humans based on the cumulative permeation across a Caco-2 monolayer or rat intestine. Our newly developed system enables more kinds of oral preparations and also pH-dependent soluble drugs to be evaluated.
  • Shirou Itagaki, Mitsuru Sugawara, Michiya Kobayashi, Sachiho Nishimura, Michio Fujimoto, Katsumi Miyazaki, Ken Iseki
    European journal of pharmacology 475 1-3 85 - 92 2003年08月15日 [査読有り][通常論文]
     
    Phenolsulfonphthalein is used for testing renal function. However, its excretion mechanism has not been elucidated. The purpose of this study was therefore to elucidate the transporter-mediated excretion system for phenolsulfonphthalein. p-Aminohippuric acid, a substrate of rat organic anion transporter1 (rOat1), and cimetidine, a substrate of rOat3, reduced the urinary excretion of phenolsulfonphthalein. The uptake of phenolsulfonphthalein by kidney slices was found to consist of two components. The IC50 values of rOat1 substrates were higher than those of rOat3 substrates. In the presence of cimetidine, the Eadie-Hofstee plot gave a single straight line. The profile of the phenolsulfonphthalein uptake component in the presence of cimetidine was similar to that of the low-affinity component in the absence of cimetidine. We conclude that rOat1 and rOat3 are involved in the renal uptake of phenolsulfonphthalein and that phenolsulfonphthalein is a high-affinity substrate for rOat3 but is a relatively low-affinity substrate for rOat1.
  • 笠原 勇太, 高田 陽美, 小林 道也, 川合 真次, 荻野 修, 菅原 満, 関川 彬, 宮崎 勝巳
    医療薬学 29 2 165 - 172 (一社)日本医療薬学会 2003年04月 [査読有り][通常論文]
  • Mitsuru Sugawara, Toru Ogawa, Michiya Kobayashi, Katsumi Miyazaki
    Biochimica et biophysica acta 1609 1 39 - 44 2003年01月10日 [査読有り][通常論文]
     
    The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined. The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study. However, the uptake of both substrates was not inhibited by glycine, an amino acid. The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine (countertransport effect). On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake. The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2. This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney.
  • 岸野 吏志, 越浪 由加, 菅原 満, 丸藤 哲, 古川 博之, 藤堂 省, 宮崎 勝巳
    TDM研究 20 1 24 - 29 (一社)日本TDM学会 2003年01月 [査読有り][通常論文]
     
    生体部分肝移植後患者3例を対象に標題の血中動態を検討した.CHDF施行時と非施行時の全血中タクロリムス濃度に有意な違いは認めなかった.ダイアライザーの流入側,流出側のタクロリムス濃度にも違いは認められなかった.又,CHDF非施行例との間に体内動態パラメーターの有意な違いは認めなかった.これらより,CHDFの血中タクロリムス濃度への影響は極めて小さいと考えられた
  • SUGAWARA Mitsuru, KATO Masaya, KITAKUBO Mayumi, TAKEKUMA Yoh, GANAPATHY Vadivel, MIYAZAKI Katsumi
    Drug metabolism and pharmacokinetics 18 3 186 - 93 日本薬物動態学会 2003年 [査読有り][通常論文]
     
    To elucidate the mechanism of the interaction of basic drugs with Na+-dependent L-alanine absorption from the small intestine, we investigated the effect of imipramine on the transport of L-alanine via system B0, which is thought to be one of the main Na+-dependent systems for intestinal absorption of short-chain neutral amino acids, including L-alanine. The uptake of L-alanine by cells that express hATB0 (human amino acid transporter B0) was inhibited in the presence of imipramine. The Eadie-Hofstee plot showed that the inhibition was not competitive with the substrate (L-alanine) but competitive with Na+. When rat intestinal brush border membrane vesicles were used, several basic drugs had inhibitory effects. Inhibition was also observed in intestinal absorption evaluated by an in situ single-pass perfusion technique. However, the potencies of inhibition were different. The potency of inhibition was dependent on the lipophilicity of the drugs.
  • Shirou Itagaki, Mitsuru Sugawara, Michiya Kobayashi, Katsumi Miyazaki, Ken Iseki
    Drug metabolism and pharmacokinetics 18 4 238 - 44 2003年 [査読有り][通常論文]
     
    Phenolsulfonphthalein (PSP) has been selected as a model drug that is eliminated from both the kidney and liver in rats. Although the renal PSP transport system has been studied, few details of the biliary excretion of PSP have been reported. We investigated the biliary excretion system for PSP in rats. It has been reported that the biliary excretion of many organic anions from hepatocytes into bile is mediated by a primary active transporter, referred to as multidrug resistance-associated protein 2 (Mrp2/abcc2). The biliary excretion of PSP in SD rats was significantly decreased in the presence of Mrp2 inhibitors. The biliary excretion of PSP in Eisai hyperbilirubinemic rats (EHBR), hereditarily Mrp2-defective rats, was significantly lower than that in SD rats. Moreover, an efflux experiment using Caco-2 cells was carried out to confirm Mrp2-mediated PSP transport. Mrp2 inhibitors significantly decreased PSP efflux from Caco-2 cells. These results suggest that Mrp2 contributes to the biliary excretion of PSP in SD rats.
  • M Sugawara, T Ogawa, M Kobayashi, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1609 1 39 - 44 2003年01月 [査読有り][通常論文]
     
    The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined. The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study. However, the uptake of both substrates was not inhibited by glycine, an amino acid. The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine (countertransport effect). On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake. The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2. This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney. (C) 2002 Elsevier Science B.V. All rights reserved.
  • Satoshi Kishino, Akikazu Nomura, Shin Itoh, Tsutomu Nakagawa, Yoh Takekuma, Mitsuru Sugawara, Hiroyuki Furukawa, Satoru Todo, Katsumi Miyazaki
    European journal of clinical pharmacology 58 9 621 - 8 2002年12月 [査読有り][通常論文]
     
    OBJECTIVE: Alpha(1)-acid glycoprotein (AAG) is a major binding protein for neutral and basic drugs because of its great drug affinity. AAG has three main genetic variants--F1, S, and A variants. Several attempts have been made to elucidate the differences in compositions of the carbohydrate moiety and structure-function relationships such as drug-binding differences. However, there have been few reports on age- and gender-related differences in compositions or concentrations of the carbohydrate moiety of AAG variants. The aim of this study was to clarify the age- and gender-related differences in carbohydrate concentrations and in drug-binding capacities of AAG glycoforms. METHODS: The sera used in this study were obtained from 32 healthy subjects (17 men and 15 women, aged 16-84 years). The AAG glycoforms were isolated by hydroxyapatite chromatography. The binding capacity of AAG to disopyramide (DP), which is a basic drug, was determined using the ultrafiltration method. The concentrations of N-acetylneuraminic acid (NeuAc) and monosaccharides in AAG were determined using high-pH anion-exchange chromatography with pulsed-amperometric detection. RESULTS: The mean plasma AAG concentration in the female subjects was significantly lower than that in the male subjects (0.67 +/- 0.12 mg/ml, mean +/- SD, in females, n = 15, versus 0.81 +/- 0.17 mg/ml in males, n = 17, P < 0.05), but no age-related differences were found (0.75 +/- 0.18 mg/ml in young subjects, n = 24, versus 0.77 +/- 0.12 mg/ml in older subjects, n = 8, n.s.). However, the degree of branching of the glycan chain in the female subjects was significantly lower than that in the male subjects (1.61 +/- 0.17 mol/mol, mean +/- SD, in females, n = 15, versus 1.75 +/- 0.23 mol/mol in males, n = 17, P < 0.05). There was a significant inverse relationship between the binding capacity of AAG to DP (Cb/AAG) and the degree of branching of the glycan chain. The binding capacity (Cb/AAG) decreased as the degree of branching in AAG glycans increased. The binding capacity (Cb/AAG) in the female subjects was significantly higher than that in the male subjects (2.79 +/- 0.59 mg/g AAG in females, mean +/- SD, n = 15, versus 2.37 +/- 0.29 mg/g AAG in males, n = 17, P < 0.05). CONCLUSION. The degree of branching of the glycan chain in AAG plays an important role in drug-binding capacity. Gender-related differences in drug-binding capacity (Cb/AAG) may be caused by differences in the ratios of the extent of branching of the glycan chain in AAG.
  • Satoshi Kishino, Yoh Takekuma, Mitsuru Sugawara, Tsuyoshi Shimamura, Hiroyuki Furukawa, Satoru Todo, Katsumi Miyazaki
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 780 2 289 - 94 2002年11月25日 [査読有り][通常論文]
     
    We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics.
  • Mitsuru Sugawara, Megumi Kurosawa, Kasumi Sakai, Michiya Kobayashi, Ken Iseki, Katsumi Miyazaki
    Biochimica et biophysica acta 1564 1 149 - 55 2002年08月19日 [査読有り][通常論文]
     
    The effects of transmembrane electric potential difference and ionic strength on the permeation of tryptamine and indoleacetic acid across a Caco-2 cell monolayer were examined. A decrease in the transmembrane electric potential difference caused by the addition of potassium ion to the transport buffer had no effect on the permeation rate of either compound. On the other hand, an increase in ionic strength resulted in a decrease in the permeation rate of tryptamine and an increase in the permeation rate of indoleacetic acid. The changes in the permeation rate with changes in the ionic strength were correlated with the membrane surface potential monitored by 1-anilino-8-naphthalenesulfonic acid (ANS), a fluorescent probe. We tested these effects using several other cationic and anionic compounds. These effects of ionic strength were found to be common to all drugs tested. The compound that showed a relatively lower permeation rate was given relatively stronger effect. The possibility of overestimation or underestimation caused by these effects should be considered when the permeation of an ionic compound is evaluated using a cell monolayer system.
  • M Sugawara, M Kurosawa, K Sakai, M Kobayashi, K Iseki, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1564 1 149 - 155 2002年08月 [査読有り][通常論文]
     
    The effects of transmembrane electric potential difference and ionic strength on the permeation of tryptamine and indoleacetic acid across a Caco-2 cell monolayer were examined. A decrease in the transmembrane electric potential difference caused by the addition of potassium ion to the transport buffer had no effect on the permeation rate of either compound. On the other hand, an increase in ionic strength resulted in a decrease in the permeation rate of tryptamine and an increase in the permeation rate of indoleacetic acid. The changes in the permeation rate with changes in the ionic strength were correlated with the membrane surface potential monitored by 1-anilino-8-naphthalenesulfonic acid (ANS), a fluorescent probe. We tested these effects using several other cationic and anionic compounds. These effects of ionic strength were found to be common to all drugs tested. The compound that showed a relatively lower permeation rate was given relatively stronger effect. The possibility of overestimation or underestimation caused by these effects should be considered when the permeation of an ionic compound is evaluated using a cell monolayer system. (C) 2002 Elsevier Science B.V. All rights reserved.
  • 菅原 満, 萩野 修, 宮崎 勝巳
    医療薬学 28 3 256 - 258 (一社)日本医療薬学会 2002年06月 [査読有り][通常論文]
  • 井藤達也, 福田由布子, 竹本 功, 斉藤正信, 松岡伸一, 秦 温信, 平野 剛, 井関 健, 菅原 満, 宮崎勝巳
    臨床薬理 33 3 67 - 72 2002年 [査読有り][通常論文]
     
    We investigated the absorption rates of acetaminophen, theophyline and lansoprazole after pylorus preserving-gastrectomy (PPG) with preservation of the vagal nerve as a treatment for patients with early gastric cancer. Postoperative functioning of the residual stomach 6 months after the operation in patients with early gastric cancer who had undergone PPG (PPG group, n=5) was compared with that in patients who had undergone distal gastrectomy (DG group, n=4). We also investigated recovery of body weight, findings in a series of gastrointestinal x-rays, gastroscopic findings, hormonal secretion and digestive and absorbtive abilities. The postoperative absorption rates of acetaminophen in the PPG group were almost the same as those before the operation, but they were slower in the PPG group than in the DG group. The absorption rate of theophyline from a sustained release formulation was faster in the DG group, and slower in the PPG group compared to the preoperative absorption rates. In the DG group, the absorption rate of an enteric-coated preparation of lansoprazole did not differ greatly from that before the operation. In the PPG group, however, there were large individual differences and a notable delay in absorption and reduction in the amount of absorption in the early stage. Recovery of body weight at 6 months after the operation was not significantly different in the PPG and DG groups. In the PPG group, postoperative gastrointestinal x-rays showed that the pyloric form had been retained, and gastroscopic examination showed that there had been no reflux gastritis or esophagitis. The rates of digestion and absorption were faster in the DG group than in the PPG group, and the plasma levels of glucose were higher but the serum levels of gastrin were lower in the DG group than in the PPG group. Furthermore, hormonal secretion in the PPG group was close to the normal physiological range. These results indicate that the rate of absorption was faster in the DG group and slower in the PPG group. The absorbability of drugs following gastric resection varies depending on the type of operation and the properties of the drug preparation.
  • 井藤達也, 高岡和夫, 竹本 功, 秦 温信, 井上勝一, 佐々木健太郎, 平野 剛, 井関 健, 菅原 満, 宮崎勝巳
    臨床薬理 33 2 47 - 52 2002年 [査読有り][通常論文]
     
    The purpose of this study was to evaluate the distribution of CPT-11 and its active metabolite, SN-38, in pleural and pericardial fluid after intravenous administration. Two patients with lung cancer were treated with intravenous CPT-11 (60 mg/m2) on days 1, 8, and 15. The CPT-11 was detected in the pleural fluid 1.5 hr after the begining of intravenous infusion, and the level reached the maximum 24 hrs later. Similarly, the active metabolite SN-38 was detected in the pleural fluid 1.5 hr after the begining of intravenous infusion, and SN-38 concentration in the pleural fluid was almost as high as that in plasma 24 hrs later. These results suggest that intravenously administered CPT-11 may penetrate the thoracic cavity and may be metabolized to SN-38 there. The proportions of maximum concentrations of CPT-11 and SN-38 in the pleural fluid to the corresponding plasma levels were 20.4% and 28.5%, respectively. In addition, the AUCs of the lactone form SN-38 were much lower than those of the carboxyl form in the pleural fluid. CPT-11, SN-38 and SN-38 glucronide showed similar pharmacokinetics in the pericardium as that in plasma.
  • T Nakanishi, R Kekuda, YJ Fei, T Hatanaka, M Sugawara, RG Martindale, FH Leibach, PD Prasad, Ganapathy, V
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 281 6 C1757 - C1768 2001年12月 [査読有り][通常論文]
     
    We have cloned a new subtype of the amino acid transport system N2 (SN2 or second subtype of system N) from rat brain. Rat SN2 consists of 471 amino acids and belongs to the recently identified glutamine transporter gene family that consists of system N and system A. Rat SN2 exhibits 63% identity with rat SN1. It also shows considerable sequence identity (50-56%) with the members of the amino acid transporter A subfamily. In the rat, SN2 mRNA is most abundant in the liver but is detectable in the brain, lung, stomach, kidney, testis, and spleen. When expressed in Xenopus laevis oocytes and in mammalian cells, rat SN2 mediates Na+-dependent transport of several neutral amino acids, including glycine, asparagine, alanine, serine, glutamine, and histidine. The transport process is electrogenic, Li+ tolerant, and pH sensitive. The transport mechanism involves the influx of Na+ and amino acids coupled to the efflux of H+, resulting in intracellular alkalization. Proline, alpha-(methylamino) isobutyric acid, and anionic and cationic amino acids are not recognized by rat SN2.
  • M Kobayashi, N Sada, M Sugawara, K Iseki, K Miyazaki
    INTERNATIONAL JOURNAL OF PHARMACEUTICS 221 1-2 87 - 94 2001年06月 [査読有り][通常論文]
     
    A new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract was developed. In this new system, a drug (solid form) is added into a drug-dissolving vessel (pH 1.0) and the dissolved drug is transferred to a pH adjustment vessel (pH 6.0). Then the drug solution is transferred to the apical surface of Caco-2 cells, and the permeation rate of the: drug across a Caco-2 monolayer is determined. This system was able to predict the oral absorption ratios of ten water-soluble drugs in humans. Using this system, it was predicted that drugs that permeated Caco-2 at a rate of more than 0.1%, of the dose in 200 min would be almost completely absorbed after oral administration in humans. For a drug whose permeation ratio was less than 0.03%, the absorption ratio was predicted to be less than 30%,. This system also enabled prediction of the absorption rate and variability in the absorption of albendazole, a drug with poor water solubility. It also enabled assessment of the improvement in absorption using a solid dispersion of albendazole-polymers that improved the water solubility. The results suggest that this system is useful for oral absorption screening of new drugs and pharmaceutical products. (C) 2001 Elsevier Science B.V. All rights reserved.
  • R Ling, CC Bridges, M Sugawara, T Fujita, FH Leibach, PD Prasad, Ganapathy, V
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1512 1 15 - 21 2001年05月 [査読有り][通常論文]
     
    We investigated the molecular mechanism involved in the adaptive regulation of the amino acid transport system Al a process in which amino acid starvation induces the transport activity. These studies were done with rat C6 glioma cells. System A activity in these cells is mediated exclusively by the system A subtype, amino acid transporter A2 (ATA2). The other two known system A subtypes, ATA1 and ATA3, are not expressed in these cells. Exposure of these cells to an amino acid-free medium induces system A activity. This process consists of an acute phase and a chronic phase. Laser-scanning confocal microscopic immunolocalization of ATA2 reveals that the acute phase is associated with recruitment of preformed ATA2 from an intracellular pool to the plasma membrane. In contrast, the chronic phase is associated with an induction of nta gene expression as evidenced from the increase in the steady-state levels of ATA2 mRNA, restoration of the intracellular pool of ATA2 protein, and blockade of the induction by cycloheximide and actinomycin D. The increase in system A activity induced by amino acid starvation is blocked specifically by system A substrates, including the non-metabolizable alpha-(methylamino)isobutyric acid. (C) 2001 Elsevier Science B.V. All rights reserved.
  • T Nakanishi, M Sugawara, W Huang, RG Martindale, FH Leibach, ME Ganapathy, PD Prasad, Ganapathy, V
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 281 5 1343 - 1348 2001年03月 [査読有り][通常論文]
     
    We have cloned a new subtype of the amino acid transport system N from a human liver cell line. This transporter, designated SN2, consists of 472 amino acids and exhibits 62% identity with human SN1 at the level of amino acid sequence. SN2-specific transcripts are expressed predominantly in the stomach, brain, liver, lung, and intestinal tract. The sizes of the transcripts vary in different tissues, indicating tissue-specific alternative splicing of the SN2 mRNA. In contrast, SN1 is expressed primarily in the brain and liver and there is no evidence for the presence of multiple transcripts of varying size for SN1. When expressed in mammalian cells, the cloned human SN2 mediates Na+-coupled transport of system N-specific amino acid substrates (glutamine, asparagine, and histidine). In addition, SN2 also transports serine, amino, and glycine. Anionic amino acids, cationic amino acids, imino acids, and N-alkylated amino acids are not recognized as substrates by human SN2. The SN2-mediated transport process is Li+ tolerant and highly pH-dependent. The Michaelis-Menten constant for histidine uptake via human SN2 is 0.6 +/- 0.1 mM, The gene coding for SN2 is located on human chromosome Xp11.23. Successful cloning of SN2 provides the first molecular evidence for the existence of subtypes within the amino acid transport system N in mammalian tissues. (C) 2001 Academic Press.
  • T Hatanaka, W Huang, R Ling, PD Prasad, M Sugawara, FH Leibach, Ganapathy, V
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1510 1-2 10 - 17 2001年02月 [査読有り][通常論文]
     
    We report here on the cloning and functional characterization of the third subtype of amino acid transport system A, designated ATA3 (amino acid transporter A3), from a human liver cell line. This transporter consists of 547 amino acids and is structurally related to the members of the glutamine transporter family. The human ATA3 (hATA3) exhibits 88% identity in amino acid sequence with rat ATA3. The gene coding for hATA3 contains 16 exons and is located on human chromosome 12q13. It is expressed almost exclusively in the liver. hATA3 mediates the transport of neutral amino acids including alpha-(methylamino)isobutyric acid (MeAIB), the model substrate for system A, in a Na+-coupled manner and the transport of cationic amino acids in a Na+-independent manner. The affinity of hATA3 for cationic amino acids is higher than for neutral amino acids. The transport function of hATA3 is thus similar to that of system y(+)L. The ability of hATA3 to transport cationic amino acids with high affinity is unique among the members of the glutamine transporter family. hATA1 and hATA2, the other two known members of the system A subfamily, show little affinity toward cationic amino acids. hATA3 also differs from hATA1 and hATA2 in exhibiting low affinity for MeAIB. Since liver does not express any of the previously known high-affinity cationic amino acid transporters, ATA3 is likely to provide the major route for the uptake of arginine in this tissue. (C) 2001 Elsevier Science B.V. All rights reserved.
  • M Sugawara, T Nakanishi, YJ Fei, RG Martindale, ME Ganapathy, FH Leibach, Ganapathy, V
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1509 1-2 7 - 13 2000年12月 [査読有り][通常論文]
     
    To date, two different transporters that are capable of transporting alpha-(methylamino)isobutyric acid, the specific substrate for amino acid transport system A, have been cloned. These two transporters are known as ATA1 and ATA2. We have cloned a third transporter that is able to transport the system A-specific substrate. This new transporter, cloned from rat skeletal muscle and designated rATA3, consists of 547 amino acids and has a high degree of homology to rat ATA1 (47% identity) and rat ATA2 (57% identity). rATA3 mRNA is present only in the liver and skeletal muscle. When expressed in Xenopus laevis oocytes, rATA3 mediates the transport of alpha-[C-14](methylamino)isobutyric acid and [H-3]alanine. With the two-microelectrode voltage clamp technique, we have shown that exposure of rATA3-expressing oocytes to neutral, short-chain aliphatic amino acids induces inward currents. The amino acid-induced current is Na+-dependent and pH-dependent. Analysis of the currents with alanine as the substrate has shown that the K-0.5 for alanine (i.e., concentration of the amino acid yielding half-maximal current) is 4.2 +/- 0.1 mM and that the Na+:alanine stoichiometry is 1:1. (C) 2000 Elsevier Science B.V. All rights reserved.
  • イリノテカンと活性代謝物のラクトン体・カルボキシル体およびその抱合体のHPLC同時定量法の確立
    井藤達也, 竹本 功, 秦 温信, 高岡和夫, 菅原 満, 井関 健, 宮崎勝巳
    TDM研究 17 4 383 - 389 2000年10月 [査読有り][通常論文]
  • YJ Fei, M Sugawara, T Nakanishi, W Huang, HP Wang, PD Prasad, FH Leibach, Ganapathy, V
    JOURNAL OF BIOLOGICAL CHEMISTRY 275 31 23707 - 23717 2000年08月 [査読有り][通常論文]
     
    We have cloned the human Na+- and H+-coupled amino acid transport system N (hSN1) from HepG2 liver cells and investigated its functional characteristics. Human SN1 protein consists of 504 amino acids and shows high homology to rat SN1 and rat brain glutamine transporter (GlnT). When expressed in mammalian cells, the transport function of human SN1 could be demonstrated with glutamine as the substrate in the presence of LiCl (instead of NaCl) and cysteine. The transport activity was saturable, pH-sensitive, and specific for glutamine, histidine, asparagine, and alanine. Analysis of Li+ activation kinetics showed a Li+:glutamine stoichiometry of 2:1. When expressed in Xenopus laevis oocytes, the transport of glutamine or asparagine via human SN1 was associated with inward currents under voltage-clamped conditions. The transport function, monitored as glutamine- or asparagine-induced currents, was saturable, Na+-dependent, Li+-tolerant, and pH-sensitive. The transport cycle was associated with the involvement of more than one Na+ ion. Uptake of asparagine was directly demonstrable in these oocytes by using radiolabeled substrate, and this uptake was inhibited by membrane depolarization. In addition, simultaneous measurement of asparagine influx and charge influx in the same oocyte yielded an asparagine:charge ratio of 1. These data suggest that SN1 mediates the influx of two Na+ and one amino acid substrate per transport cycle coupled to the efflux of one H+, rendering the transport process electrogenic.
  • Sugawara M, Nakanishi T, Fei Y.-J, Huang W, Ganapathy M. E, Leibach F. H, Ganapathy V
    J. Biol. Chem. 275 22 16473 - 16477 2000年08月 [査読有り][通常論文]
     
    We report here on the cloning and functional characterization of the protein responsible for the system A amino acid transport activity that is known to be expressed in most mammalian tissues. This transporter, designated ATA2 for amino acid transporter A2, was cloned from rat skeletal muscle. It is distinct from the neuron-specific glutamine transporter (GlnT/ATA1). Rat ATA2 consists of 504 amino acids and bears significant homology to GlnT/ATA1 and system N (SN1). ATA2-specific mRNA is ubiquitously expressed in rat tissues. When expressed in mammalian cells, ATA2 mediates Na+dependent transport of α-(methylamino)isobutyric acid, a specific model substrate for system A. The transporter is specific for neutral amino acids. It is pH- sensitive and Li+-intolerant. The Na+:amino acid stoichiometry is 1:1. When expressed in Xenopus laevis oocytes, transport of neutral amino acids via ATA2 is associated with inward currents. The substrate-induced current is Na+-dependent and pH-sensitive. The amino acid transport system A is particularly known for its adaptive and hormonal regulation, and therefore the successful cloning of the protein responsible for this transport activity represents a significant step toward understanding the function and expression of this transporter in various physiological and pathological states.
  • Hatanaka T, Huang W, Wang H, Sugawara M, Prasad P. D, Leibach F. H, Ganapathy V
    Biochim. Biophys. Acta 1467 1 1 - 6 2000年07月 [査読有り][通常論文]
  • HP Wang, W Huang, M Sugawara, LD Devoe, FH Leibach, PD Prasad, Ganapathy, V
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 273 3 1175 - 1179 2000年07月 [査読有り][通常論文]
     
    This report describes the primary structure and functional characteristics of human ATA1, a subtype of the amino acid transport system A. The human ATA1 cDNA was isolated from a placental cDNA library. The cDNA codes for a protein of 487 amino acids with 11 putative transmembrane domains. The transporter mRNA (similar to 9.0 kb) is expressed most prominently in the placenta and heart, but detectable level of expression is evident in other tissues including the brain. When expressed heterologously in mammalian cells, the cloned transporter mediates Na+-coupled transport of the system A-specific model substrate alpha-(methylamino)isobutyric acid. The transport process is saturable with a Michaelis-Menten constant of 0.89 +/- 0.12 mM. The Na+:amino acid stoichiometry is 1:1 as deduced from the Na+-activation kinetics. The transporter is specific for small short-chain neutral amino acids. The gene for the transporter is located on human chromosome 12, (C) 2000 Academic Press.
  • T Hatanaka, W Huang, HP Wang, M Sugawara, PD Prasad, FH Leibach, Ganapathy, V
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1467 1 1 - 6 2000年07月 [査読有り][通常論文]
     
    We report here on the primary structure and functional characteristics of the protein responsible for the system A amino acid transport activity that is known to be expressed in most human tissues. This transporter, designated ATA? for amino acid transporter A2, was cloned from the human hepatoma cell line HepG2. Human ATA2 (hATA2) consists of 506 amino acids and exhibits a high degree of homology to rat ATA2. hATA2-specific mRNA is ubiquitously expressed in human tissues. When expressed in mammalian cells, hATA2 mediates Na+-dependent transport of alpha-(methylamino)isobutyric acid, a specific model substrate for system A. The transporter is specific for neutral amino acids. It is pH-sensitive and Li+-intolerant. The Na+-amino acid stoichiometry is 1:1. (C) 2000 Elsevier Science B.V. All rights reserved.
  • YJ Fei, M Sugawara, JC Liu, HW Li, Ganapathy, V, ME Ganapathy, FH Leibach
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1492 1 145 - 154 2000年06月 [査読有り][通常論文]
     
    We describe in this report the cDNA structure, functional characteristics, genomic organization, and promoter analysis of the mouse H+-coupled low-affinity peptide transporter PEPT1. The mouse PEPT1 cDNA cloned from a kidney cDNA library is similar to 3.1 kb long and encodes a protein of 709 amino acids. When expressed heterologously in mammalian cells and in Xenopus laevis oocytes, mouse PEPT1 mediates H+-coupled electrogenic transport of the dipeptide glycylsarcosine. The mouse pept1 gene, cloned from a genomic DNA library in bacterial artificial chromosome, is similar to 38 kb long and consists of 23 exons and 22 introns. 5'-Rapid amplification of cDNA ends with poly(A)(+) RNA from mouse intestine has identified the transcription start site that lies 31 bp upstream of the translation start site. The promoter region upstream of the transcription start site does not contain the TATA box but possesses three GC boxes which are the binding sites for the transcription activator SP1. Functional analysis of the promoter region using the luciferase reporter assay in Caco-2 cells (a human intestinal cell line that express PEPT1 constitutively) and five different 5'-deletion fragments of the promoter has shown that essential promoter/enhancer elements are present within 1140 bp upstream of the transcription start site. (C) 2000 Elsevier Science B.V. All rights reserved.
  • M Sugawara, W Huang, YL Fei, FH Leibach, Ganapathy, V, ME Ganapathy
    JOURNAL OF PHARMACEUTICAL SCIENCES 89 6 781 - 789 2000年06月 [査読有り][通常論文]
     
    In clinical trials, valganciclovir, the valyl ester of ganciclovir, has been shown to enhance the bioavailability of ganciclovir when taken orally by patients with cytomegalovirus infection. We investigated the role of the intestinal peptide transporter PEPT1 in this process by comparing the interaction of ganciclovir and valganciclovir with the transporter in different experimental systems. We also studied the interaction of these two compounds with the renal peptide transporter PEPT2. In cell culture model systems using Caco-2 cells for PEPT1 and SKPT cells for PEPT2, valganciclovir inhibited glycylsarcosine transport mediated by PEPT1 and PEPT2 with Ki values (inhibition constant) of 1.68 +/- 0.30 and 0.043 +/- 0.005 mM, respectively. The inhibition by valganciclovir was competitive in both cases. Ganciclovir did not interact with either transporter. Similar studies done with cloned PEPT1 and PEPT2 in heterologous expression systems yielded comparable results. The transport of valganciclovir via PEPT1 was investigated directly in PEPT1-expressing Xenopus laevis oocytes with an electrophysiological approach. Valganciclovir, but not ganciclovir, induced inward currents in PEPT1-expressing oocytes. These results demonstrate that the increased bioavailability of valganciclovir is related to its recognition as a substrate by the intestinal peptide transporter PEPT1. This prodrug Is also recognized by the renal peptide transporter PEPT2 with high affinity. (C) 2000 Wiley-Liss, Inc.
  • Ganapathy M. E, Huang W, Rajan D. P, Carter A. L, Sugawara M, Iseki K, Leibach F. H, Ganapathy V
    J. Biol. Chem. 275 3 1699 - 1707 2000年01月 [査読有り][通常論文]
     
    Therapeutic use of cephaloridine, a beta-lactam antibiotic, in humans is associated with carnitine deficiency. A potential mechanism for the development of carnitine deficiency is competition between cephaloridine and carnitine for the renal reabsorptive process. OCTN2 is an organic cation/carnitine transporter that is responsible for Na+-coupled transport of carnitine in the kidney and other tissues. We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines. The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport, These antibiotics possess a quaternary nitrogen as does carnitine, Several other beta-lactam antibiotics that do not possess this structural feature did not interact with OCTN2, The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine, Interestingly, many of the beta-lactam antibiotics that were not recognized by OCTN2 were good substrates for the H+-coupled peptide transporters PEPT1 and PEPT2, In contrast, cephaloridine, cefoselis, cefepime, and cefluprenam, which were recognized by OCTN2, did not interact with PEPT1 and PEPT2, The interaction of cephaloridine with OCTN2 was Na+-dependent, whereas the interaction of cefoselis and cefepime with OCTN2 was largely Na+-independent, Furthermore, the Na+-dependent, OCTN2-mediated cellular uptake of cephaloridine could be demonstrated by direct uptake measurements, These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney.
  • M Kobayashi, H Fujisaki, M Sugawara, K Iseki, K Miyazaki
    PHARMACEUTICAL RESEARCH 16 12 1888 - 1892 1999年12月 [査読有り][通常論文]
     
    Purpose. To elucidate the effects of drug interactions on the urinary excretion of trientine in rats. Method. Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brush-border membrane vesicles. Results. Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide: and furosemide. which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles. Conclusions. There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.
  • 高速液体クロマトグラフィーによる血清中ピルニカイジド定量法の確立と有効濃度の検討
    井藤達也, 福島紘司, 尾形仁子, 中川英久, 渡辺 晃, 菅原 満, 井関 健, 宮崎勝巳
    TDM研究 16 3 273 - 278 1999年07月 [査読有り][通常論文]
  • Iseki K, Sugawara M, Sato K, Naasani I, Hayakawa T, Kobayashi M, Miyazaki K
    J. Pharmacol. Exp. Ther. 289 1 66 - 71 1999年04月 [査読有り][通常論文]
     
    To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles. The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar. The results provide an evidence that several transporters with different features are potentially responsible for the uptake of beta-lactam antibiotics into the intestinal cells. It is suggested that the dianionic beta-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption.
  • M Kobayashi, H Fujisaki, M Sugawara, K Iseki, K Miyazaki
    JOURNAL OF PHARMACY AND PHARMACOLOGY 51 3 279 - 284 1999年03月 [査読有り][通常論文]
     
    This study was aimed at determining the driving force for spermine transport in rat renal proximal tubular brush-border membrane. The uptake of spermine and trientine, a spermine-like drug used for treating Wilson's disease, into rat renal brush-border membrane vesicles was significantly stimulated by an outwardly directed Na+ gradient. The Na+-dependent uptake was temperature dependent and saturable. A kinetic analysis of the initial uptake of spermine with an Na+ gradient gave a K-m value of 1.44 mu M and a V-max value of 6.31 pmol (mg protein)(-1)/30 s. The Na+-dependent uptake of [H-3]spermine was inhibited by spermine, trientine and tetraethylenepentamine. Substrates of the H+/organic cation transporter (cimetidine and tetraethylammonium), physiological polyamines (putrescine and spermidine) with 2 or 3 amino groups and aminoglycosides (amikacin and tobramicin) with 4 or 5 cationic amines did not affect the uptake of spermine in the presence of an outwardly directed Na+ gradient. These results suggest that the renal tubular secretion of spermine is mediated by an Na+/spermine antiport system which is specific for a straight-chain polyamine compound with more than 4 amino groups.
  • M Sugawara, Y Takekuma, H Yamada, M Kobayashi, K Iseki, K Miyazaki
    JOURNAL OF PHARMACEUTICAL SCIENCES 87 8 960 - 966 1998年08月 [査読有り][通常論文]
     
    A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusion technique. The drugs used in this study were divided into three groups for regression analysis, and a smaller "test" set of compounds was used to assess the predictive capacity of the regression equation. When the analysis was applied to each respective group of drugs (i.e., anionic, cationic, and nonionized compounds), obtained regression coefficients were 0.569, 0.821, 0.728 by using the organic solvent (n-octanol)/buffer partition coefficient, 0.730, 0.734, 0.914 using the permeation rate across a silicon membrane, and 0.790, 0.915, 0.941 using an EVA membrane, respectively. However, smaller regression coefficients of 0.377, 0.468, and 0.718 were obtained when these three groups of drugs were put together for prediction. Meanwhile, correlation was improved remarkably when drug-membrane electrostatic interactions, namely, hydrogen-bonding donor (H-alpha) and acceptor (H-beta) activity or index of electricity (E-c), were added to the other parameters of lipophilicity and permeation rate across the EVA membrane (r = 0.880 and 0.883, respectively). Moreover, the equation obtained from these regression analyses was applicable even to the prediction of the absorption of the zwitterionic drugs. These results suggest that including the electrostatic interaction parameters in addition to lipophilicity and permeability across artificial membranes would afford a better prediction for the intestinal absorption of the vast majority of drugs.
  • 血液透析患者におけるランソプラゾールの薬物動態
    井藤達也, 稲垣真実子, 福島紘司, 岡本延彦, 安田卓二, 布施川尚, 菅原 満, 井関 健, 宮崎勝巳
    TDM研究 15 3 259 - 265 1998年07月 [査読有り][通常論文]
  • K Iseki, T Hirano, K Tsuji, S Miyazaki, M Takada, M Kobayashi, M Sugawara, K Miyazaki
    JOURNAL OF PHARMACY AND PHARMACOLOGY 50 6 627 - 634 1998年06月 [査読有り][通常論文]
     
    The mechanism of uptake of sparfloxacin, a new quinolone, by intestinal brush-border membrane vesicles was investigated to clarify whether there is a common transport process for new quinolones mediated by the diffusion potential across the intestinal membrane bilayer. Sparfloxacin was taken up pH-dependently by rat intestinal brush-border membrane vesicles, behaviour analogous to that of organic cations including enoxacin and ciprofloxacin. Transient overshooting uptake of this quinolone was observed in the presence of an outward H+ gradient. Momentary dissipation of the H+ gradient by addition of carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone did not affect the uptake of sparfloxacin, and a marked but incomplete reduction in the H+-sensitive overshooting uptake of sparfloxacin was apparent in the voltage-clamped brush-border membrane vesicles. Furthermore, a valinomycin-induced K+-diffusion potential (interior negative) and an inward Cl(-)diffusion potential stimulated the initial uptake of sparfloxacin at pH 5.5. Sparfloxacin uptake was inhibited by tetracaine and imipramine. The inhibitory effect of these cations correlated well with changes in membrane surface charges induced by the presence of tetracaine or imipramine. These results indicate that sparfloxacin transport across the brush-border membrane depends upon the inside-negative ionic diffusion potential, that the H+ - or K+-diffusion-potential-dependent uptake of sparfloxacin by intestinal brush-border membrane vesicles is affected by the membrane surface potential and that inhibition of sparfloxacin uptake originates from changes in the membrane surface potential caused by the organic cations.
  • M Sugawara, M Kato, M Kobayashi, K Iseki, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1370 2 252 - 258 1998年03月 [査読有り][通常論文]
     
    The mechanism of the inhibitory effect of imipramine, a lipophilic organic cation on the Na+-dependent transport of L-glutamic acid across intestinal brush-border membrane was investigated. The uptake of L-glutamic acid by intestinal brush-border membrane vesicles was dependent on the concentration of Na+. Fitting of the uptake; data in the presence of various concentrations of Na+ using Hill equation yielded a Hill coefficient of 2.18. This result suggest that the carrier system of L-glutamic acid has at least two sites for Na+-binding. By the analysis of double reciprocal plot and Dixon-type plot, it was found that imipramine inhibits the transport of L-glutamic acid by interacting competitively with the binding sites of Na+, but not inhibit L-glutamic acid binding site. Moreover, the effect of imipramine on the transport of L-alanine and D-glucose which are co-transported with only one Na+ molecule was also suggestive of interaction with the Na+-binding sites on the carrier. These results indicate that the mechanism of the inhibitory effect of imipramine on the Na+-dependent carrier systems is common for all systems regardless of the stoichiometry or substrates. (C) 1998 Elsevier Science B.V.
  • K Iseki, K Yonemura, T Kikuchi, Naasani, I, M Sugawara, M Kobayashi, N Kohri, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1370 1 161 - 168 1998年03月 [査読有り][通常論文]
     
    The transport activity of ceftibuten, a dianionic peptide-like compound, was extracted from rat intestinal brush-border membrane by iz-octylglucoside and reconstituted into asolectin liposomes by dialysis. The proteoliposomes prepared from the membrane extract showed an inward H+-gradient-dependent uptake of ceftibuten and glycylsarcosine. Ceftibuten-immobilized affinity chromatography of the membrane extract permitted the isolation of two polypeptides (apparent molecular mass of 117 and 127 kDa) that can recognize the dianionic peptide structure of ceftibuten. Proteoliposomes prepared from reconstituting the isolated proteins into asolectin vesicles showed an overshooting uptake of ceftibuten in the presence of an inwardly directed H+ gradient, and this uptake could be inhibited by L-valyl-L-proline. N-glycanase digestion of the isolated proteins, 117 and 127 kDa, trimmed them into 78 and 120 kDa products, respectively. The protein core size of the smaller protein was in agreement with the calculated molecular mass of similar to 79 kDa for the rat PepT1 transporter obtained by other investigators. (C) 1998 Elsevier Science B.V.
  • K Iseki, Naasani, I, T Kikuchi, M Sugawara, M Kobayashi, N Kohri, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1368 2 329 - 337 1998年01月 [査読有り][通常論文]
     
    The carrier protein(s) responsible for the transport of ceftibuten, a peptide-like dianionic cefem, in rat renal brush-border membrane were solubilized and purified by a ceftibuten-ligand specific affinity chromatography technique. The proteoliposomes reconstituted from the solubilized brush-border membrane proteins by dialysis had H+-sensitive uptake of ceftibuten and trans-stimulative effect by cephalexin. A specific uptake activity for ceftibuten was found in the 3.5 M-eluted fraction but not the flowthrough and the 0.5 M-eluted fraction of the affinity chromatography. Analyzing this active fraction by SDS/PAGE after reconstituting into liposomes gave two major proteins (approx. molecular masses of 130 and 107 kDa). The purification protocol presented in this study permitted an efficient isolation of the carrier proteins responsible for the transport of ceftibuten and other peptide-like compounds. (C) 1998 Elsevier Science B.V.
  • Satoshi Kishino, Akikazu Nomura, Michiyo Saitoh, Mitsuru Sugawara, Ken Iseki, Akira Kitabatake, Katsumi Miyazaki
    Journal of Chromatography B: Biomedical Applications 703 1-2 1 - 6 1997年12月05日 [査読有り][通常論文]
     
    A single-step isolation method for the glycoforms of human serum α1- acid glycoprotein (AAG) using a hydroxylapatite column under a gradient elution program was developed. The concentrations of N-acetylneuraminic acid and monosaccharides (fucose, N-acetylglucosamine, galactose and mannose) of six AAG glycoforms were determined by the pulsed-amperometric detection method. For each AAG glycoform, significant sex-related differences in carbohydrate content have been observed only for AAG glycoforms two and six, and not for each AAG glycoform. The relationship between the extent of the branch in the glycan chain and the binding capacity to disopyramide were examined. Female AAG contained highly sialylated AAG glycoforms compared to male glycoforms. Conversely, male AAG was rich in the lower sialylated AAG glycoform. Furthermore, it was found that the drug binding capacity decreases with increasing branching of the glycan chain. This suggests that the binding sites of AAG are hindered by a relatively large carbohydrate moiety, such as tetraantennary structures.
  • Kishino S, Nomura A, Saitoh M, Sugawara M, Iseki K, Kitabatake A, Miyazaki K
    J. Chromatogr. B 703 1-2 1 - 6 1997年12月 [査読有り][通常論文]
     
    A single-step isolation method for the glycoforms of human serum alpha(1)-acid glycoprotein (AAG) using a hydroxylapatite column under a gradient elution program was developed. The concentrations of N-acetylneuraminic acid and monosaccharides (fucose, N-acetylglucosamine, galactose and mannose) of six AAG glycoforms were determined by the pulsed amperometric detection method, For each AAG glycoform, significant sex-related differences in carbohydrate content have been observed only for AAG glycoforms two and six, and not for each AAG glycoform. The relationship between the extent of the branch in the glycan chain and the binding capacity to disopyramide were examined. Female AAG contained highly sialylated AAG glycoforms compared to male glycoforms. Conversely, male AAG was rich in the lower sialylated AAG glycoform. Furthermore, it was found that the drug binding capacity decreases with increasing branching of the glycan chain. This suggests that the binding sites of AAG are hindered by a relatively large carbohydrate moiety, such as tetraantennary structures.
  • K Iseki, K Kaido, M Kobayashi, M Sugawara, K Miyazaki
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 20 7 794 - 799 1997年07月 [査読有り][通常論文]
     
    The effect of membrane surface potential of the apical side on the intracellular uptake of ionic compounds was investigated using the human colon adenocarcinoma cell line (Caco-2). The transepithelial transport of indolepropionic acid and tryptamine was consistent with the uptake behavior shown by rat intestinal brush-border membrane (BBM) vesicles. Imipramine, which diminished the negative charge of the membrane surface (for both Caco-2 and BBM), acted to increase the uptake of the anionic compounds, indolepropionic acid and ceftibuten, and to decrease that of tryptamine (cationic compound) by both the Caco-2 monolayer and the intestinal BBM vesicles at a pH of 7.5. These results suggest that the effects of membrane surface potential on the permeability of ionic compounds were detectable on the Caco-2 cell line as well as the BBM vesicles. On the other hand, the inhibition of H+-linked transport and the stimulation of the surface charge-regulated uptake of ceftibuten have occurred simultaneously on the Caco-2 cell line in the presence of imipramine. It seems that the membrane surface charge (negative) plays an important role in the transport process of ionic compounds across the intestinal epithelium.
  • M Kobayashi, S Suruga, H Takeuchi, M Sugawara, K Iseki, K Miyazaki
    JOURNAL OF PHARMACY AND PHARMACOLOGY 49 5 511 - 515 1997年05月 [査読有り][通常論文]
     
    The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated. A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.
  • M Kobayashi, R Tanabe, M Sugawara, K Iseki, K Miyazaki
    JOURNAL OF PHARMACY AND PHARMACOLOGY 49 4 426 - 429 1997年04月 [査読有り][通常論文]
     
    Trientine dihydrochloride is used to treat Wilson's disease by chelating copper and increasing its urinary excretion. The mechanism of renal excretion of trientine has been investigated in-vivo and in-vitro. Trientine clearance in the rat was significantly faster than creatinine clearance. When trientine and the same number of moles of copper ions were administered simultaneously to the rat, however, trientine clearance decreased to almost the same level as the creatinine clearance. To clarify this active excretion system for trientine, the uptake of trientine and a physiological polyamine compound, spermine, was investigated using rat renal brush-border membrane vesicles. Although, because trientine and spermine are organic cations, the H+/organic cation transporter is expected to recognize these compounds, neither an outwardly directed H+ gradient nor an inward Na+ gradient stimulated trientine uptake. [C-14]Spermine uptake was, nevertheless, trans-stimulated by both unlabelled spermine and trientine and the trans-stimulating effect of spermine on trientine uptake was, furthermore, completely abolished by addition of copper ions to the incubation medium. These results suggest that there is a specific transport system for spermine and trientine on the renal brush-border membrane. This transport system contributes to the secretion of trientine in the kidney proximal tubule but does not recognize the trientine-copper complex.
  • Naasani, I, T Kikuchi, M Sugawara, M Kobayashi, K Iseki, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1283 2 185 - 191 1996年09月 [査読有り][通常論文]
     
    Optimal procedures for the reconstitution of the transport activity of ceftibuten, a dianionic beta-lactam antibiotic, from rat kidney brush-border membrane were developed. The uptake activity into reconstituted proteoliposomes appeared to be particularly sensitive to the extraction conditions, and to the lipid composition used for reconstitution. Changes in the concentration of octyl glucoside significantly affected the extraction of ceftibuten transport activity, and optimal extraction was achieved at a concentration of 60 mM. Optimal reconstitution was achieved using a lipid composition of asolectin, cholesterol and phosphatidylserine in a w/w percent ratio of 60:30:10, respectively, and with a lipid-to-protein ratio of 10. The uptake of ceftibuten into the resulting proteoliposomes showed temperature and pH dependency, was inhibitable by a range of cephem antibiotics, oligopeptides and the organic anion PAH, and was trans-stimulated by cephalexin and dipeptides. This reconstitution system will likely prove useful in future studies on the functional analysis of the peptide transport system in a purified form.
  • R Tanabe, M Kobayashi, M Sugawara, K Iseki, K Miyazaki
    JOURNAL OF PHARMACY AND PHARMACOLOGY 48 5 517 - 521 1996年05月 [査読有り][通常論文]
     
    The uptake characteristics of trientine by rat intestinal brush-border membrane vesicles were studied. The uptake characteristics of trientine were similar to those of the physiological polyamines with respect to the excessive accumulation in vesicles, the pH dependency, the temperature dependency and the ineffectiveness of K+ diffusion potential (inside negative). The initial uptake of trientine was saturable with a K-m value of 1.13 mM, which was larger than that of spermine and spermidine. Furthermore, the uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Spermine competitively inhibited the uptake of trientine with a K-i value of 18.6 mu M, and it was close to the K-m value for spermine (30.4 mu M). These data suggested that the uptake of trientine was similar to that of spermine and spermidine in rat small intestinal brush-border membrane vesicles, and these polyamines seem to inhibit the absorption of trientine from the gastrointestinal tract.
  • 井関 健, 中垣 悌, 小林道也, 菅原 満, 荻野 修, 宮崎勝巳
    病院薬学 22 2 183 - 188 日本病院薬剤師会 1996年03月 [査読有り][通常論文]
     
    A method for predicting pH changes in multiple admixtures was designed on the basis of the acid-base equilibrium theory. The pH's of transfusions mixed with the various injections were estimated by solving a general theoretical equation for proton concentrations in the multicomponents-blended aquaous solution obtained using a dichotomy as the algorithm. Eighty-two transfusions and parenteral solution mixture combinations were examined for the efficacy of the predicted equation. As a result, the estimated pH was in good agreement with the measured pH in all examinations, and a good corelation existed between the measured and calculated values of pH. Furthermore, the incompatibility of the parenteral admixture can be easily predicted using the present estimation-program for pH changes without any preliminary pH titration tests. These results suggest that this prediction method will be a useful tool for constructing and handling database incompatipility.
  • Iseki K, Sugawara M, Fujiwara T, Naasani I, Kobayashi M, Miyazaki K
    Biochim. Biophys. Acta 1278 1 105 - 110 1996年01月 [査読有り][通常論文]
  • K Iseki, M Sugawara, T Fujiwara, Naasani, I, M Kobayashi, K Miyazaki
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1278 1 105 - 110 1996年01月 [査読有り][通常論文]
     
    Na+-driven nucleoside transport processes across rat intestinal brush-border membrane vesicles were investigated. 6-Mercaptopurine riboside (6-MPR), an analogue of purine-nucleoside such as adenosine and inosine, was recognized by its purine- and pyrimidine-nucleosides transport system, but their nucleo-bases did not entirely inhibit the 6-MPR transport. The analysis according to the Hill equation of the curve for Na+ activation of 6-MPR uptake was consistent with the notion of a Na+/6-MPR coupling stoichiometry of 1:1. The expressed transport activities of adenosine, uridine, and 6-MPR were Na+-dependent and saturable, and their affinity constants (K-m value) obtained by Eadie-Hofstee analysis were approx. 20, 15 and 100 mu M. Moreover, the uptake of radiolabeled adenosine and uridine was trans-stimulated by 6-MPR inside vesicles in the absence of an inwardly directed Na+-gradient. On the other hand, uridine did not exhibit any inhibitory effects on the uptake of adenosine despite the fact that adenosine was a potent inhibitor for uridine uptake by intestinal brush-border membrane vesicles. These differences in the inhibition may be explained by the multiplicity of the nucleoside transport systems.
  • Kishino S, Nomura A, Sugawara M, Iseki K, Kakinoki S, Kitabatake A, Miyazaki K
    J. Chromatogr. B 672 2 199 - 205 1995年10月 [査読有り][通常論文]
     
    A simple purification method for human plasma alpha-1-acid glycoprotein (AAG) using an ion-exchange and hydroxyapatite column was developed. The recovery of the method was found to be high. We also improved a determination method for N-acetylneuraminic acid and monosaccharides in the carbohydrate moiety of AAG by using an ion-exchange column and pulse-amperometric detection. By this method, a composition analysis of the carbohydrate moiety of AAG (N-acetylneuraminic acid, fucose, N-acetyl glucosamine, galactose and mannose) was possible with 1.0 ml of plasma. We compared these carbohydrate concentrations in the AAG of patients with renal insufficiency with those of healthy subjects. In the AAG of the patients, the concentrations of N-acetylglucosamine, galactose and mannose were significantly higher than those in the AAG of the healthy subjects.
  • S KISHINO, A NOMURA, ZS DI, M SUGAWARA, K ISEKI, S KAKINOKI, A KITABATAKE, K MIYAZAKI
    THERAPEUTIC DRUG MONITORING 17 5 449 - 453 1995年10月 [査読有り][通常論文]
     
    The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (K-d). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.
  • T HIRANO, K ISEKI, SATO, I, S MIYAZAKI, M TAKADA, M KOBAYASHI, M SUGAWARA, K MIYAZAKI
    PHARMACEUTICAL RESEARCH 12 9 1299 - 1303 1995年09月 [査読有り][通常論文]
     
    Purpose. To clarify the absorption-structure relationship for the fluoroquinolones from the point of view of inhibitory behavior. Methods, The inhibitory effects of ciprofloxacin on the transport process of enoxacin across the rat intestinal blush-border membrane was examined. Results, Ciprofloxacin, which has a similar structure to enoxacin, exhibited a pH-dependent interference with enoxacin absorption from rat jejunal loops. The uptake experiments using BBM vesicles showed that ciprofloxacin significantly reduced not only the initial binding of enoxacin to the membrane surface, hut also the K+- or H+-diffusion potential-dependent transport across the membrane. Furthermore, an H+-diffusion potential (interior negative) also exhibited a stimulative uptake of ciprofloxacin. Conclusions. These results suggest that the inhibition behavior of ciprofloxacin from the jejunal loop was closely related to the ionic diffusion potential-dependent uptake of enoxacin across the brush-border membrane.
  • NAASANI, I, K SATO, K ISEKI, M SUGAWARA, M KOBAYASHI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 1231 2 163 - 168 1995年09月 [査読有り][通常論文]
     
    The transport characteristics of ceftibuten, a dianionic cephem antibiotic, in rat renal and intestinal brush-border membranes were compared. Ceftibuten transport was mediated by two transport systems in the renal brush-border membrane and by one transport system in the intestinal brush-border membrane. The apparent kinetic parameters for the uptake of ceftibuten by the renal brush-border membrane vesicles, respectively, were: K-m1, K-m2 values of 26 and 1946 mu M and V-max1, V-max2 values of 105 and 1400 pmol/mg protein per 30 s. The apparent kinetic parameters for the uptake by the intestinal brush-border membrane vesicles were: K-m of 425 mu M and V-max of 1701 pmol/mg protein per 30 s. In the renal brush-border membrane, L-Ala-L-Pro was partially competitive and competitive inhibitor for the uptake by the high and low affinity systems, respectively. However, L-Ala-L-Pro was a non-competitive inhibitor for the uptake by the intestinal brush-border membrane vesicles. L-Carnosine was a specific and competitive inhibitor for the high affinity system in the renal brush-border membrane, while it had no effect on the low affinity system of the kidney or on the transport system of the intestine. It was concluded that the transport characteristics of ceftibuten in the renal and intestinal brush-border membranes are similar in some aspects but they are not identical.
  • S KISHINO, A NOMURA, ZS DI, M SUGAWARA, K ISEKI, S KAKINOKI, A KITABATAKE, K MIYAZAKI
    JOURNAL OF CLINICAL PHARMACOLOGY 35 5 510 - 514 1995年05月 [査読有り][通常論文]
     
    Age- and gender-related changes in serum alpha(1)-acid glycoprotein (AAG) concentration and the serum protein binding of disopyramide were examined after intensive medical examination. Based on the clinical chemistry tests over 51 points, 245 subjects were diagnosed as healthy and 71 subjects (22.5%) revealed an abnormal value for at least one item, In the healthy subjects, serum AAG concentration in men was significantly higher than in women (men, 0.78 +/- 0.18 mg/mL, mean +/- SD; women, 0.67 +/- 0.16 mg/mL. In contrast, there were no significant differences in the AAG concentration between age groups for men and women and in the unbound fraction of disopyramide. Gender changes AAG concentration. Age, however, does not change AAG concentration and the protein binding of the basic drug.
  • NAASANI, I, M SUGAWARA, M KOBAYASHI, K ISEKI, K MIYAZAKI
    PHARMACEUTICAL RESEARCH 12 4 605 - 608 1995年04月 [査読有り][通常論文]
     
    The uptake mechanism of ceftibuten by rat renal brush-border membrane vesicles was investigated. Uptake was found to be independent of a Na+ gradient and partially dependent on an inwardly directed H+-gradient. Competition experiments between ceftibuten and several compounds demonstrated that the peptide-like structural features of inhibitors are more essential than their charge properties for inhibiting uptake. Anionic compound, such as p-aminohippuric acid, also inhibited ceftibuten uptake by renal brush-border membrane vesicles in the presence of an H+-gradient. We conclude that ceftibuten, in spite of its anionic structure, is transported via the dipeptide transport systems, rather than the organic anion transport system.
  • Sugawara M, Oikawa H, Kobayashi M, Iseki K, Miyazaki K
    Biochim. Biophys. Acta 1234 1 22 - 28 1995年03月 [査読有り][通常論文]
  • M SUGAWARA, H OIKAWA, M KOBAYASHI, K ISEKI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1234 1 22 - 28 1995年03月 [査読有り][通常論文]
     
    The effect of membrane surface potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was investigated. In the presence of an inside-negative K+-diffusion potential, the manner of initial uptake of tryptamine appeared to be pi-I-dependent and the uptake in the acidic medium was lower than that in the neutral medium. Changes in surface potential of brush-border membrane vesicles were monitored using 8-anilino-1-naphthalenesulfonic acid (ANS) and the results suggested that the membrane surface potential (negative charge on the membrane surface) decreased in the acidic medium. A good correlation was observed between the K+-diffusion potential-dependent uptake of tryptamine and membrane surface potential monitored by ANS at various pH levels. The uptake of tryptamine by liposomes (large unilamellar vesicles), which contained various amounts of dipalmitoylphosphatidylserine (DPPS), was also examined. The uptake of tryptamine decreased with a decrease of DPPS content in the liposomes, and was correlated with the membrane surface potential monitored by ANS. Moreover, the effect of organic cations on the uptake of tryptamine by intestinal brush-border membrane vesicles was examined. The uptake of tryptamine was inhibited by tetracaine and imipramine. The inhibitory effect of these cations was well correlated with changes in the membrane surface potential in the presence of tetracaine or imipramine. These results suggest that the Kf-diffusion potential-dependent uptake of tryptamine by intestinal brush-border membrane vesicles is affected by membrane surface potential, and the inhibition of tryptamine uptake originates in changes in the membrane surface potential caused by the organic cations.
  • T HIRANO, K ISEKI, M SUGAWARA, S MIYAZAKI, M TAKADA, K MIYAZAKI
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 18 2 342 - 346 1995年02月 [査読有り][通常論文]
     
    The mechanism of the renal transport of enoxacin (ENX) has been investigated using brush-border membrane vesicles (BBMV's) isolated from the rat renal cortex. The initial rate and time-course of ENX uptake were quite dependent upon the medium pH (pH 5.5 > pH 7.5). The pH dependence was in accordance with the degree of cationic form. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H+-gradient. The initial uptake Has saturable, and transport kinetic parameters were given for a K-m and V-max of 0.59 mM and 1.37 nmol/(mg protein)/30 s, respectively. On the other hand, an outward H+-gradient (pH(in)=5.5, (out)=7.5) dependent uptake of ENX was partially decreased by the voltage-clamped BBMVs. Furthermore, a valinomycin-induced K+-diffusion potential (interior negative) was found to increase the uptake of ENX at pH 5.5,, which is cationic form-rich. These results suggest that ENX uptake participates in not only the H+/organic cation antiport system for organic cation secretion but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.
  • Mitsuru Sugawara, Yoh Takekuma, Michiya Kobayashi, Ken Iseki, Katsumi Miyazaki
    Pharmacy and Pharmacology Communications 1 10 491 - 493 1995年 [査読有り][通常論文]
     
    A method for predicting the intestinal absorption of anionic drugs by measuring their physicochemical properties (organic solvent/buffer partition coefficients, hydrogen bonding and diffusion rate across silicone membrane) was investigated. The absorption rates of ten anionic drugs, which were mainly non‐steroidal anti‐inflammatory agents, were measured in‐situ by a rat intestinal single‐pass perfusion technique. A poor correlation between the absorption rate and the partition into octanol was observed, although the absorption rate showed a tendency to increase when the partition coefficient increased. On the other hand, the technique of determining the permeation rate across silicon membrane, which comprises a diffusion process, gave a good correlation with the in‐situ absorption results. The effects of permeant size (molecular volume or molecular weight) and hydrogen bonding were also investigated. When these two factors were considered together with the permeation rate across a silicone membrane, excellent regression coefficients were obtained. These results suggest that the permeation rate across a silicone membrane, permeant size and hydrogen bonding are valuable measures for predicting the absorption behaviour of anionic drugs. 1995 Royal Pharmaceutical Society of Great Britain
  • MICHIYA KOBAYASHI, RYOU TANABE, MITSURU SUGAWARA, KEN ISEKI, KATSUMI MIYAZAKI
    Pharmacy and Pharmacology Communications 1 7 337 - 339 1995年 [査読有り][通常論文]
     
    The uptake characteristics of polyamines were investigated using basolateral membrane vesicles isolated from rat small intestine. Only putrescine uptake was stimulated by an inward Na+ gradient. A kinetic analysis of the initial uptake of putrescine with Na+ gradient gave a Km value of 1.95 μm and a Vmax value of 6.01 pmol (mg protein)−130s. Several diamine compounds including methylglyoxal bis‐(guanyl)hydrazone, an antileukemia reagent, inhibited the putrescine uptake. However, tri‐ and tetraamine compounds such as spermine and spermidine did not. These results suggested that there is a specific carrier for putrescine in the basolateral membrane of rat small intestinal epithelial cells. This carrier recognizes some compounds with two cationic amino groups. Taking into account the difference of the concentration of sodium ion between the intra‐ and the extra‐cellular spaces, this carrier will transport putrescine from the blood to the intestinal cells. 1995 Royal Pharmaceutical Society of Great Britain
  • KEN ISEKI, IMAD NAASANI, MITSURU SUGAWARA, TOSHIE FUJIWARA, MICHIYA KOBAYASHI, KATSUMI MIYAZAKI
    Pharmacy and Pharmacology Communications 1 3 127 - 129 1995年 [査読有り][通常論文]
     
    The transport systems of 6‐mercaptopurine riboside (6‐MPR), a nucleoside analogue, in the human jejunal brush‐border membrane and in the human epithelial cell line, Caco‐2, were investigated. The transport activities of 6‐MPR were found to be dependent upon an inward Na+‐gradient at pH 5·5. Trans‐stimulation studies indicated that the uptakes of both [3H]adenosine and [3H]uridine were significantly increased by the presence of 6‐MPR inside the human brush‐border membrane vesicles. The uptake of 6‐MPR from the apical side of Caco‐2 monolayer was sensitive for an inward‐directed Na+‐gradient, and a greater uptake was observed at an acidic medium (pH 5·5> 7·5). Moreover, both adenosine and uridine were significantly effective in inhibiting the 6‐MPR uptake by Caco‐2. These results indicate that an analogue of adenosine, 6‐MPR, is able to be taken up via the Na+‐gradient‐dependent purine‐ and pyrimidine‐nucleosides transport systems in the human intestinal brush‐border membrane. 1995 Royal Pharmaceutical Society of Great Britain
  • T HIRANO, K ISEKI, S MIYAZAKI, M TAKADA, M KOBAYASHI, M SUGAWARA, K MIYAZAKI
    JOURNAL OF PHARMACY AND PHARMACOLOGY 46 8 676 - 679 1994年08月 [査読有り][通常論文]
     
    Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H+-gradient. Momentary dissipation of the H+-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K+-diffusion potential induced by valinomycin. Furthermore, not only the outward H+-gradient but also an inward Cl--gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl--gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H+-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.
  • M SUGAWARA, T TODA, M KOBAYASHI, K ISEKI, K MIYAZAKI, H SHIROTO, JI UCHINO, Y KONDO
    JOURNAL OF PHARMACY AND PHARMACOLOGY 46 8 680 - 684 1994年08月 [査読有り][通常論文]
     
    The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H+-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent K-m and V-max values of 0.35 mM and 2.052 nmol (mg protein)(-1) min(-1) for human BBMV, and 0.50 mM and 3.056 nmol (mg protein)(-1) min(-1) for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver-Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.
  • Sugawara M, Hashimoto A, Kobayashi M, Iseki K, Miyazaki K
    Biochim. Biophys. Acta 1192 2 241 - 246 1994年06月 [査読有り][通常論文]
  • M SUGAWARA, A HASHIMOTO, M KOBAYASHI, K ISEKI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1192 2 241 - 246 1994年06月 [査読有り][通常論文]
     
    The effect of membrane surface potential on the uptake of several anionic compounds by liposomes (large unilamellar vesicles), which contain various amounts of dipalmitoylphosphatidylserine (DPPS), was investigated. The uptake amount of four tested anionic compounds (cefixime, benzyioxyindoleacetic acid (BOIAA), ceftibuten and S-1006) decreased with an increase in the DPPS content of liposomes, and was correlated with the membrane surface potential monitored using a fluorescent dye, 8-anilino-1-naphthalene sulfonate (ANS). Moreover, for all of the tested anionic compounds, a good correlation was observed between the ratio of the uptake value (5 min) by each of the liposomes comprising various amounts of DPPS to the uptake value by liposomes containing 10% DPPS and a relative membrane surface potential monitored by ANS. On the other hand, the uptake of zwitterionic compounds (enoxacin, cephradine and benzyloxytryptophan (BOTP)) was independent of DPPS content. These results suggest that the uptake of tested anionic compounds by large unilamellar lipid vesicles is dependent on the membrane surface potential which originates in the surface negative charge.
  • 井関 健, 佐藤 佳子, 菅原 満
    薬学雑誌 114 4 233 - 240 (公社)日本薬学会 1994年04月 [査読有り][通常論文]
     
    1)ペプチド製剤エンテルード(R)は,CETBの吸収を顕著に遅らせた。しかし,CEXの吸収には何ら変化が認められなかったことより,両薬物の消化管吸収に違いのあることが明らかになった。2)エンテルード(R)の吸収抑制効果は,主成分であるペプチドによる輸送担体の阻害ではなく,その他の構成成分によって生じることが認められた
  • K ISEKI, Y SATOH, M SUGAWARA, K MIYAZAKI
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN 114 4 233 - 240 1994年04月 [査読有り][通常論文]
     
    The effect of simultaneous administration of Enterued (R), an elemental diet, which is composed of oligopeptides (egg white hydrolyzate), on the orally active cefems was investigated. Ceftibuten (CETB) administered together with Enterued (R) to man was excreted slower in the urine. AUC from the plasma concentrations of CETB after the oral administration with Enterued (R) was markedly decreased compared to that without Enterued (R) in rat. In contrast, neither urinary excretion of cephalexin (CEX) in man nor the AUC from the plasma profile of CEX in rat was changed by Enterued (R). Furthermore, the disappearance, tissue accumulation, net absorption of CETB from the rat jejunal loop were significantly inhibited by Enterued (R). However, the net absorption of CEX has no alternation in the presence of Enterued (R), although the apparent disappearance decreased on the basis of the diminishment of tissue accumulation. Additionally, Hepan ED (R), which is an elementary diet composed of amino acids, and the mineral solution containing neither peptides nor vitamins have also exhibited the decreasing effect on the CETB absorption behaviour. These results suggested that the inhibitory effects of Enterued (R) on the absorption of these antibiotics were not due to the inhibition of peptide-transport systems.
  • Sugawara M, Hashimoto A, Toda T, Takahashi M, Kobayashi M, Iseki K, Miyazaki K
    Biochim. Biophys. Acta 1190 1 85 - 90 1994年02月 [査読有り][通常論文]
  • M SUGAWARA, A HASHIMOTO, T TODA, M TAKAHASHI, M KOBAYASHI, K ISEKI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1190 1 85 - 90 1994年02月 [査読有り][通常論文]
     
    The effects of membrane surface potential on the uptake of anionic compounds by rat intestinal brush-border membrane vesicles were investigated. The uptake amount of all tested anionic compounds (ceftibuten, cefixime, benzylpenicillin, s-1006 and rentiapril) in the neutral medium (pH 7.5) was lower than that in the acidic medium (pH 5.5). Changes in surface potential of brush-border membrane vesicles were monitored using a fluorescence dye, 8-anilino-1-naphthalenesulfonate (ANS), and the results suggested an increase of a negative charge on the membrane surface proportional to the increase of the pH of medium. A good correlation was observed between the initial uptake rate of all tested anionic compounds and relative membrane surface potential monitored by ANS. Moreover, the uptake of cefixime by artificial liposome made from PC containing various amount of DPPS was measured. The uptake value of cefixime was decreased in proportion to an increase of DPPS content. These results suggest that the permeation of anionic compounds across intestinal brush-border membrane is dependent on surface potential originate in the surface negative charge.
  • Ken Iseki, Mitsuru Sugawara, Nobutaka Saitoh, Katsumi Miyazaki
    BBA - Biomembranes 1152 1 9 - 14 1993年10月10日 [査読有り][通常論文]
     
    Further investigation of organic cation transport mechanisms were continued using rat intestinal brush-border membranes following our previous report [1,2]. The net uptake of organic cations was superior to that of their zwitterionic derivatives. This result agreed with the absorption behaviour of these compounds from rat intestinal loop. The uptake of tyramine and 5-benzyloxytryptamine was significantly stimulated by the valinomycin-generated K+-diffusion potential (inside-negative). On the other hand, the uptake of zwitterionic derivatives was not affected by the valinomycin-induced K+-diffusion potential. The voltage-clamped brush-border membrane vesicles exhibited a complete disappearance of the overshoot-uptake of organic cations. Therefore, this permeation mechanism across the intestinal brush-border membrane seems to be different from the well-known H+-antiport system of organic cation found in other organs such as kidney and liver, and depends upon an inside-negative H+- or K+-diffusion potential. © 1993.
  • K ISEKI, M SUGAWARA, N SAITOH, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA 1152 1 9 - 14 1993年10月 [査読有り][通常論文]
     
    Further investigation of organic cation transport mechanisms were continued using rat intestinal brush-border membranes following our previous report [1,2]. The net uptake of organic cations was superior to that of their zwitterionic derivatives. This result agreed with the absorption behaviour of these compounds from rat intestinal loop. The uptake of tyramine and 5-benzyloxytryptamine was significantly stimulated by the valinomycin-generated K+-diffusion potential (inside-negative). On the other hand, the uptake of zwitterionic derivatives was not affected by the valinomycin-induced K+-diffusion potential. The voltage-clamped brush-border membrane vesicles exhibited a complete disappearance of the overshoot-uptake of organic cations. Therefore, this permeation mechanism across the intestinal brush-border membrane seems to be different from the well-known H+-antiport system of organic cation found in other organs such as kidney and liver, and depends upon an inside-negative H+- or K+-diffusion potential.
  • Michiya Kobayashi, Ken Iseki, Mitsuru Sugawara, Katsumi Miyazaki
    BBA - Biomembranes 1151 2 161 - 167 1993年09月19日 [査読有り][通常論文]
     
    Na+-independent uptake rate and binding to the membrane surface of polyamines (spermine, spermidine and putrescine) have been characterized using rat small intestinal brush-border membrane vesicles. The uptake of spermine and spermidine was saturable (Km 30.4 μM and 148.1 μM, respectively), however, putrescine uptake was not saturable up to 8 mM. In contrast, the values of binding to the membrane surface of all polyamines were not saturable in the present studies. In Dixon plot analysis, spermine competitively inhibited the uptake rate of spermidine with a Ki value of 33.8 μM, while the putrescine inhibitory effect on the spermidine uptake rate was non-competitive (Ki 3.28 mM). These uptake systems were not affected by the valinomycin-induced K+-diffusion potential (inside negative). These results suggested that there were two different Na+-independent uptake systems for spermine and spermidine, as well as for putrescine, on this membrane. However, they were not the same as the electric potential-dependent uptake system for monocationic compounds. Furthermore, this uptake system for spermine and spermidine might not be a carrier protein, because the intravesicular spermine exhibited no trans-stimulation effect on the uptake of spermidine. © 1993.
  • Kobayashi M, Iseki K, Sugawara M, Miyazaki K
    Biochim. Biophys. Acta 1151 2 161 - 167 1993年09月 [査読有り][通常論文]
  • M KOBAYASHI, K ISEKI, M SUGAWARA, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA 1151 2 161 - 167 1993年09月 [査読有り][通常論文]
     
    Na+-independent uptake rate and binding to the, membrane surface of polyamines (spermine, spermidine and putrescine) have been characterized using rat small intestinal brush-border membrane vesicles. The uptake of spermine and spermidine was saturable (K(m) = 30.4 muM and 148.1 muM, respectively), however, putrescine uptake was not saturable up to 8 mM. In contrast, the values of binding to the membrane surface of all polyamines were not saturable in the present studies. In Dixon plot analysis, spermine competitively inhibited the uptake rate of spermidine with a K(i) value of 33.8 muM, while the putrescine inhibitory effect on the spermidine uptake rate was non-competitive (K(i) = 3.28 mM). These uptake systems were not affected by the valinomycin-induced K+-diffusion potential (inside negative). These results suggested that there were two different Na+-independent uptake systems for spermine and spermidine, as well as for putrescine, on this membrane. However, they were not the same as the electric potential-dependent uptake system for monocationic compounds. Furthermore, this uptake system for spermine and spermidine might not be a carrier protein, because the intravesicular spermine exhibited no trans-stimulation effect on the uptake of spermidine.
  • Y TAKAHASHI, T ITOH, M KOBAYASHI, M SUGAWARA, H SAITOH, K ISEKI, K MIYAZAKI, S MIYAZAKI, M TAKADA, Y KAWASHIMA
    JOURNAL OF PHARMACY AND PHARMACOLOGY 45 5 419 - 424 1993年05月 [査読有り][通常論文]
     
    The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H+ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H+ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H+ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (K(m) and V(max) of 68.0 muM and 1.25 nmol (mg protein)-1/30 s, respectively). The stimulation of disopyramide uptake by an outward H+ gradient in rat intestinal brush-border membrane was due to an interior negative H+-diffusion potential. A K+-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.
  • ウィルソン病治療薬トリエンチンの患者における血清中濃度推移と尿中排泄挙動
    小林 道也, 長原 しのぶ, 菅原 満
    TDM研究 10 2 166 - 171 (一社)日本TDM学会 1993年04月 [査読有り][通常論文]
  • Ken Iseki, Mitsuru Sugawara, Nobutaka Saitoh, Katsumi Miyazaki
    BBA - Biomembranes 1146 1 121 - 126 1993年02月23日 [査読有り][通常論文]
     
    The uptake mechanisms of organic cations such as tryptamine, tyramine, 5-benzyloxytryptamine (BOTA) and their zwitterionic derivatives (tyrosine, tryptophan, 5-benzyloxytryptophan (BOTP)) by rat intestinal brush-border membrane vesicles and liposome containing phosphatidylserine were studied and compared. As compared to their zwitterionic derivatives, uptake rates by rat intestinal brush-border membrane of these three cations were far superior. The binding of cationic compounds to the brush-border membrane was also higher than those of their zwitterionic derivatives. Furthermore, the binding behaviour of BOTA and tryptamine to phospholipid liposome clearly amplified with increasing amounts of phosphatidylserine. In contrast, the contents of phosphatidylserine, a negatively charged phospholipid, exhibited no effects on the binding of zwitterionic derivatives (tryptophan and BOTP). The double-reciprocal plot of tryptamine binding with BOTA to liposome showed competitive inhibition. These results suggest that the binding of organic cations to the membrane lipid has a relatively high specificity despite the absence of membrane protein such as a transport-carrier in the liposome, and that the binding of cationic compounds plays an important role in the uptake to the cell membrane systems. © 1993.
  • K ISEKI, M SUGAWARA, N SAITOH, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA 1146 1 121 - 126 1993年02月 [査読有り][通常論文]
     
    The uptake mechanisms of organic cations such as tryptamine, tyramine, 5-benzyloxytryptamine (BOTA) and their zwitterionic derivatives (tyrosine, tryptophan, 5-benzyloxytryptophan (BOTP)) by rat intestinal brush-border membrane vesicles and liposome containing phosphatidylserine were studied and compared. As compared to their zwitterionic derivatives, uptake rates by rat intestinal brush-border membrane of these three cations were far superior. The binding of cationic compounds to the brush-border membrane was also higher than those of their zwitterionic derivatives. Furthermore, the binding behaviour of BOTA and tryptamine to phospholipid liposome clearly amplified with increasing amounts of phosphatidylserine. In contrast, the contents of phosphatidylserine, a negatively charged phospholipid, exhibited no effects on the binding of zwitterionic derivatives (tryptophan and BOTP). The double-reciprocal plot of tryptamine binding with BOTA to liposome showed competitive inhibition. These results suggest that the binding of organic cations to the membrane lipid has a relatively high specificity despite the absence of membrane protein such as a transport-carrier in the liposome, and that the binding of cationic compounds plays an important role in the uptake to the cell membrane systems.
  • M SUGAWARA, T TODA, K ISEKI, K MIYAZAKI, H SHIROTO, Y KONDO, JI UCHINO
    JOURNAL OF PHARMACY AND PHARMACOLOGY 44 12 968 - 972 1992年12月 [査読有り][通常論文]
     
    The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush-border membrane vesicles isolated from man, rat and rabbit was studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush-border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon). In rabbit jejunal brush-border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush-border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used. These results suggest that the transport characteristics of human and rat intestinal brush-border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of beta-lactam antibiotics.
  • Hiroshi Saitoh, Michiya Kobayashi, Mitsuru Sugawara, Ken Iseki, Katsumi Miyazaki
    BBA - Biomembranes 1112 1 153 - 160 1992年11月23日 [査読有り][通常論文]
     
    The characteristics of the intestinal transport system for choline were investigated using isolated brush-border membrane vesicles from rat small intestine. In spite of the diminutive lipid solubility, the uptake of choline by membrane vesicles reflected smooth permeation into intravesicular space rather than the binding to the membrane surface. Physiological conditions, present in the intact intestine, such as an inward-directed Na+ or H+ gradient and inside negative membrane potentials, didn't directly involve in choline transport across the brush-border membrane. Moreover, an outward-directed H+ gradient had no significant effect on the time course of choline transport. However, in the absence of a driving-force, the initial uptake of choline exhibited a saturable manner. A kinetic analysis of the initial uptake rate gave an apparent Km of 159 μM. Furthermore, unlabeled choline caused both cis-inhibition and trans-stimulation for labeled choline transport, suggesting the existence of a carrier-mediated transport system for choline, classified as so-called 'facilitated diffusion'. Since tetramethylammonium, acetylcholine, and N1-methylnicotinamide caused both cis-inhibition and trans-stimulation, they appear to be accepted as the substrate of choline carrier. On the other hand, quaternary ammonium compounds (QACs) such as those which possessed hydrophobic parts in their molecules exhibited only cis-inhibition. They also inhibited Na+-dependent d-glucose transport, indicating that they influenced various carrier-mediated transport systems non-specifically due to interaction with the membrane. These findings strongly suggest that the choline transport system on the brush-border membrane of rat intestine recognizes only small molecular QACs as its substrate. © 1992.
  • Mitsuru Sugawara, Makoto Sasaki, Ken Iseki, Katsumi Miyazaki
    BBA - Biomembranes 1111 2 145 - 150 1992年11月09日 [査読有り][通常論文]
     
    The effect of membrane potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was studied. In the presence of an outwardly directed H+-gradient, the initial uptake of tryptamine was stimulated remarkably and the overshoot phenomenon was observed. In contrast, the uptake was depressed by an inwardly-directed H+-gradient. The effect of H+-gradient on the uptake of tryptamine was maintained in the presence of FCCP, whereas it vanished when voltage-clamped vesicles were used. Moreover, the uptake of tryptamine was linearly augmented with increase of the valinomycin-induced inside-negative K+ diffusion potential. These results suggest that tryptamine is taken up into intestinal brush-border membrane vesicles depends upon the ionic diffusion potential. The effect of several indole derivatives and amine compounds on the uptake of tryptamine was also examined. The uptake of tryptamine was inibited by all amine compounds used, but anionic and zwitterionic compounds had no effect, suggesting that these amines amines interact on brush-border membrane and cause an inhibitory effect. © 1992.
  • H SAITOH, M KOBAYASHI, M SUGAWARA, K ISEKI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA 1112 1 153 - 160 1992年11月 [査読有り][通常論文]
     
    The characteristics of the intestinal transport system for choline were investigated using isolated brush-border membrane vesicles from rat small intestine. In spite of the diminutive lipid solubility, the uptake of choline by membrane vesicles reflected smooth permeation into intravesicular space rather than the binding to the membrane surface. Physiological conditions, present in the intact intestine, such as an inward-directed Na+ or H+ gradient and inside negative membrane potentials, didn't directly involve in choline transport across the brush-border membrane. Moreover, an outward-directed H+ gradient had no significant effect on the time course of choline transport. However, in the absence of a driving-force,the initial uptake of choline exhibited a saturable manner. A kinetic analysis of the initial uptake rate gave an apparent K(m) of 159 muM. Furthermore, unlabeled choline caused both cis-inhibition and trans-stimulation for labeled choline transport, suggesting the existence of a carrier-mediated transport system for choline, classified as so-called 'facilitated diffusion'. Since tetramethylammonium, acetylcholine, and N1-methylnicotinamide tinamide caused both cis-inhibition and trans-stimulation, they appear to be accepted as the substrate of choline carrier. On the other hand, quaternary ammonium compounds (QACs) such as those which possessed hydrophobic parts in their molecules exhibited only cis-inhibition. They also inhibited Na+-dependent D-glucose transport, indicating that they influenced various carrier-mediated transport systems non-specifically due to interaction with the membrane. These findings strongly suggest that the choline transport system on the brush-border membrane of rat intestine recognizes only small molecular QACs as its substrate.
  • Sugawara M, Sasaki M, Iseki K, Miyazaki K
    Biochim. Biophys. Acta 1111 2 145 - 150 1992年11月 [査読有り][通常論文]
  • Kishino S, Zai D.S, Sugawara M, Iseki K, Miyazaki K
    J. Chromatogr. 582 1-2 246 - 248 1992年11月 [査読有り][通常論文]
     
    A rapid and simple method for the determination of alpha1-acid glycoprotein (AAG) in serum was developed by using an anion-exchange column for clean-up of serum and a hydroxyapatite column for high-performance liquid chromatography (HPLC). A good correlation was observed between this HPLC method and the conventional radial immunodiffusion method. The method may also be used to determine the AAG concentration in the serum of experimental animals.
  • M SUGAWARA, M SASAKI, K ISEKI, K MIYAZAKI
    BIOCHIMICA ET BIOPHYSICA ACTA 1111 2 145 - 150 1992年11月 [査読有り][通常論文]
     
    The effect of membrane potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was studied. In the presence of an outwardly directed H+-gradient, the initial uptake of tryptamine was stimulated remarkably and the overshoot phenomenon was observed. In contrast, the uptake was depressed by an inwardly-directed H+-gradient. The effect of H+-gradient on the uptake of tryptamine was maintained in the presence of FCCP, whereas it vanished when voltage-clamped vesicles were used. Moreover, the uptake of tryptamine was linearly augmented with increase of the valinomycin-induced inside-negative K+ diffusion potential. These results suggest that tryptamine is taken up into intestinal brush-border membrane vesicles depends upon the ionic diffusion potential. The effect of several indole derivatives and amine compounds on the uptake of tryptamine was also examined. The uptake of tryptamine was inhibited by all amine compounds used, but anionic and zwitterionic compounds had no effect, suggesting that these amines interact on brush-border membrane and cause an inhibitory effect.
  • ニコランジルの血中微量定量法と血中動態
    岸野 吏志, 菅原 満, 井関 健
    TDM研究 9 2 94 - 100 (一社)日本TDM学会 1992年09月 [査読有り][通常論文]
  • K ISEKI, T HIRANO, Y FUKUSHI, Y KITAMURA, S MIYAZAKI, M TAKADA, M SUGAWARA, H SAITOH, K MIYAZAKI
    JOURNAL OF PHARMACY AND PHARMACOLOGY 44 9 722 - 726 1992年09月 [査読有り][通常論文]
     
    The mechanism of the intestinal transport of enoxacin, an orally active fluoroquinolone antibiotic, has been investigated using brush-border membrane vesicles isolated from rat small intestine. The initial rate and time-course of enoxacin uptake were considerably dependent upon the medium pH (pH 5.5 > pH 7.5) and upon the percent ionization of the carboxyl group (pK(a) 6.2, anionic charge), namely, the degree of uptake of cationic form was higher than that of the zwitterionic form. There was evidence of transport into the intravesicular space as shown by the effect of extravesicular medium osmolarity on enoxacin uptake at steady state (30 min). This transport across the brush-border membrane was stimulated by the valinomycin-induced K+-diffusion potential (interior negative) and an outward H+-diffusion potential. Furthermore, changing the pH of the medium from 5-5 to 7-5 significantly decreased the effect of valinomycin-induced K+ -diffusion potential on the enoxacin uptake. These results suggest that the uptake behaviour of the cationic form of enoxacin plays an important role in the intestinal absorption process of enoxacin.
  • M KOBAYASHI, M SUGAWARA, K ISEKI, K MIYAZAKI
    JOURNAL OF PHARMACOBIO-DYNAMICS 15 6 S67 - S67 1992年06月 [査読有り][通常論文]
  • M SUGAWARA, K ISEKI, K MIYAZAKI, H SHIROTO, Y KONDO, JI UCHINO
    JOURNAL OF PHARMACY AND PHARMACOLOGY 43 12 882 - 884 1991年12月 [査読有り][通常論文]
     
    The transport characteristics of orally active cephalosporins, ceftibuten, cefixime and cephalexin have been examined using brush border membrane vesicles isolated from human jejunum. In the initial uptake of ceftibuten, the stimulation and overshoot phenomena were observed in the presence of an inward H+ gradient. Effects of H+ gradient on the uptake of cefixime and cephalexin were low and no overshoot was observed. These transport characteristics, especially uphill transport phenomena, were in agreement with previous results obtained from rat intestinal brush-border membrane vesicles and suggest that these beta-lactam antibiotics are absorbed by different transport systems, despite their similar molecular structures.
  • Sugawara M, Iseki K, Miyazaki K
    J. Pharm. Pharmacol. 43 6 433 - 435 1991年06月 [査読有り][通常論文]
     
    The effect of an inwardly directed H+ gradient on the transport characteristics of ceftibuten, cefixime and analogues of ceftibuten in rat intestinal brush-border membrane vesicles have been investigated. In the presence of a transmembrane H+ gradient, ceftibuten and its analogues exhibited a peak to equilibrium overshoot and an accumulation in the vesicles against the concentration gradient. However, the uptake of cefixime and S-1006 [(6R, 7R)-(7-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-8-oxo-3-carbamoyloxy-methyl-5-thia-1-azabicyclo [4,2,0]oct-2-ene-2-carboxylic acid), which lacks a carboxyl group at position 4 of carboxyethylidene structure, exhibited no overshoot, although the equilibrium uptake was increased by a H+ gradient. The equilibrium uptake was dependent on the pH of the final incubation medium and the H+ gradient. These data suggested that the orally active cephalosporins were transported into rat intestinal brush-border membrane by the transmembrane H+ gradient and the pH of the medium.
  • 小林 道也, 菅原 満, 斎藤 浩司
    薬学雑誌 110 10 759 - 763 (公社)日本薬学会 1990年10月 [査読有り][通常論文]
     
    トリエンチンのより有効な投与方法を確立するための基礎的知見を得ることを目的として,ラットにおける消化管吸収および尿中排泄について検討を行った.小腸からの吸収では,トリエンチンの1時間における平均吸収率は空腸上部で42.0%,回腸部で22.5%であった.tight junction blockerであるTAPの共存下では空腸上部でのみ吸収が阻害され,回腸部では全く影響なかった.が,空腸上部でも阻害率は全吸収量の27%であり,消化管でのトリエンチンの吸収過程は小腸の上皮細胞膜の透過が主であることが示唆された.小腸刷子縁膜(BBM)に対する結合を調べると,トリエンチンは無機イオン(Na+, K+, Ca2+, Mg2+, Cu2+)非存在下ではアミノ糖抗生物質アミカシンと同程度に強く結合した.が,無機イオン存在下では結合は強く阻害され,トリエンチンのBBMに対する結合が静電気的なものであることを示唆する.食餌による吸収挙動の変化では,非絶食時の血中濃度推移は絶食時と比較して有意に低かった.トリエンチン経口投与後24時間に排泄された尿中未変化体は投与量の3%であったが,加水分解尿中のトリエンチンの総量は約35%と多く,トリエンチンの経口投与後の低い血漿中濃度は吸収性が低いことによるだけでなく,代謝を受けることにもよると考えられた.以上からトリエンチンの経口投与後の吸収は食餌内容により大きく変動すると考えられた
  • M KOBAYASHI, M SUGAWARA, H SAITOH, K ISEKI, K MIYAZAKI
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN 110 10 759 - 763 1990年10月 [査読有り][通常論文]
  • Sugawara M, Saitoh H, Iseki K, Miyazaki K, Arita T
    J. Pharm. Pharmacol. 42 5 314 - 318 1990年05月 [査読有り][通常論文]
     
    Abstract— The transport characteristics of aminopenicillins (ampicillin and amoxicillin), aminocephalosporins (cephalexin, cephradine and cefadroxil) and cefazolin have been compared with those of an actively transported substance (D‐glucose) and a passively transported substance (L‐glucose). Although the initial uptake of the aminocephalosporins was stimulated in the presence of an inward H+ gradient, there was no overshoot in the uptake of any of the drugs tested, even in the presence of an H+ gradient. Also, the time course and the degree of uptake of these drugs were similar to those of L‐glucose, especially in the absence of an H+ gradient. These results suggest that the β‐lactam antibiotics tested, like L‐glucose, pass through the rat intestinal brush border membrane mainly by passive diffusion. However, the differences in absorption between these drugs, like the differences in their disappearance from a proximal loop of rat intestine, cannot be explained by a simple permeation process alone. 1990 Royal Pharmaceutical Society of Great Britain
  • M. Sugawara, K. Iseki, H. Saitoh, K. Miyazaki, T. Arita
    Journal of Pharmacobio-Dynamics 13 4 1990年 [査読有り]
  • Iseki K, Sugawara M, Saitoh H, Miyazaki K, Arita T
    J. Pharm. Pharmacol. 41 9 628 - 632 1989年09月 [査読有り][通常論文]
     
    The transport characteristics of amino β‐lactam antibiotics, ampicillin and cephradine, have been examined and compared with that of glycylglycine using brush border membrane vesicles isolated from rat small intestine. The initial rate of glycylglycine uptake was markedly stimulated in the presence of an inward H + gradient compared with the uptake rates in the absence of an H + gradient. With the same H + gradient the stimulation of cephradine uptake was lower and ampicillin uptake was not altered. Cephradine uptake, however, was greater than that of glycylglycine in both vesicular conditions ((pH)i > (pH)0 and (pH)i = (pH)0). Inhibitory effects of dipeptides, ampicillin and cephradine on the initial uptake of glycylglycine were also examined. Glycylglycine uptake was significantly decreased in the presence of L‐phenylalanylglycine or carnosine. Ampicillin and cephradine did not alter the uptake of glycylglycine. These results suggest that the contribution of the inward H+ gradient to the permeation of ampicillin, cephradine and glycylglycine across the rat small intestinal brush border membranes is different for each of the substances examined. 1989 Royal Pharmaceutical Society of Great Britain
  • Iseki K, Sugawara M, Saitoh H, Miyazaki K, Arita T
    J. Pharm. Pharmacol. 40 10 701 - 705 1988年10月 [査読有り][通常論文]
     
    Abstract— The effect of chlorpromazine on the membrane permeability of β‐lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D‐glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25°C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D‐glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) and 1‐anilino‐8‐naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of β‐lactam antibiotics and actively transported substances in a different manner. 1988 Royal Pharmaceutical Society of Great Britain

書籍

  • 原島, 秀吉, 伊藤, 智夫, 寺田, 勝英, 伊藤, 清美 (担当:分担執筆)
    南江堂 2022年02月 (ISBN: 9784524403875) xiv, 436p
  • 吉岡, 充弘, 泉, 剛, 井関, 健, 横式, 尚司, 菅原, 満 
    医学書院 2022年01月 (ISBN: 9784260047166) 12, 361p
  • 赤池, 昭紀, 伊藤, 貞嘉, 上野, 和行, 乾, 賢一 (担当:分担執筆範囲:虚血性心疾患)
    中山書店 2020年01月 (ISBN: 9784521744520) xviii, 381p
  • 菅原, 満, 石井, 伊都子 
    南江堂 2018年03月 (ISBN: 9784524252152) xii, 145p
  • 吉岡, 充弘, 泉, 剛, 井関, 健, 横式, 尚司, 菅原, 満 
    医学書院 2018年 (ISBN: 9784260031844) 10, 352p
  • 2015年版 循環器薬の血中濃度モニタリングに関するガイドライン
    菅原 満 (担当:共著範囲:血中濃度測定法、各薬の薬物相互作用一覧)
    一般社団法人日本循環器学会 2015年
  • 菅原 満 (担当:単著範囲:臨床研究の立案と実践)
    南江堂 2015年 (ISBN: 9784524403332) ix, 231p
  • Applied 臨床薬物動態学
    菅原 満 (担当:分担執筆範囲:臨床薬物動態学総論 薬物の体内動態)
    京都廣川書店 2013年
  • 新編 プログラム学習による病態と処方解析
    菅原 満 (担当:分担執筆範囲:呼吸器疾患(急性気管支炎,肺炎))
    廣川書店 2013年
  • 実務実習テキストアルティメイト―現場で生きる学問を目指して―
    菅原 満 (担当:分担執筆範囲:第5章リスクマネージメント)
    京都廣川書店 2010年04月
  • TDM実践ハンドブック
    唯野貢司, 菅原 満, 小林道也, 齊藤嘉津彦, 後藤仁和, 戸田貴大 (担当:分担執筆)
    薬事新報社 2007年
  • 菅原, 満, 宮本, 剛典 (担当:監修)
    じほう 2005年09月 (ISBN: 4840734682) 17, 543p
  • プログラム学習による処方解析学
    菅原 満, 井関 健 (担当:分担執筆範囲:呼吸器疾患)
    廣川書店 2004年
  • 最新皮膚科学大系 特別巻1 新生児・小児・高齢者の皮膚疾患
    菅原 満, 宮崎勝巳 (担当:分担執筆範囲:新生児・小児の薬剤使用上の一般的注意、内服薬)
    中山書店 2004年
  • 医学書院 医学大事典
    菅原 満 (担当:分担執筆)
    医学書院 2003年

講演・口頭発表等

  • アレルギー性咳嗽患者に対する抗アレルギー薬の適用と治療効果に関する疫学研究  [通常講演]
    石坂 悠, 武隈 洋, 平野卓哉, 野田敏宏, 熊井恵美, 菅原 満
    第18回日本医療薬情報学会総会・学術大会(岡山) 2015年06月
  • 耳鼻咽喉科領域におけるアレルギー性咳嗽患者に対する抗アレルギー薬の適用と治療効果  [通常講演]
    武隈 洋, 石坂 悠, 平野卓哉, 野田敏宏, 熊井惠美, 菅原 満
    第64回日本アレルギー学会学術大会(東京) 2015年05月
  • 乳剤化によるコエンザイムQ10の消化管吸収改善  [通常講演]
    佐藤夕紀, 竹川悠人, 能登数馬, 武隈 洋, 菅原 満
    日本薬剤学会第30年会(長崎) 2015年05月
  • エゼチミブ(ゼチーア○Rが機能性食品成分α-トコフェノールの吸収に与える影響  [通常講演]
    梨本俊亮, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬剤学会第30年会(長崎) 2015年05月
  • TDMへの応用を目指した3種のチロシンキナーゼ阻害剤の血中濃度測定法の検証  [通常講演]
    助畑 歩, 武隈 洋, 佐藤夕紀, 鷲見正人, 田中寛之, 遠藤雅之, 菅原 満
    日本薬学会北海道支部第142回例会(札幌) 2015年05月
  • 「実践的医療薬学教育プログラム」および「チーム医療・地域医療プログラム」の開発~シンポジウム「先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発」  [通常講演]
    小澤光一郎, 中嶋幹郎, 菅原 満, 関根祐子
    日本薬学会第135年会(神戸) 2015年03月
  • Niemann-Pick C1 Like-1 (NPC1L1)を標的とした乳剤化による難吸収性物質の吸収改善  [通常講演]
    竹川悠人, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第135年会(神戸) 2015年03月
  • ローヤルゼリー機能性成分の腸管 透過性評価と吸収成分の生理機能の解析  [通常講演]
    本間直幸, 山日千明, 面すみれ, 佐藤夕紀, 菅原 満, 村田清志, 山口喜久二, 森山隆則
    第12回日本機能性食品医用学会総会(京都) 2014年12月
  • UDP-グルクロン酸転移酵素の生細胞と細胞破砕液での代謝活性の比較  [通常講演]
    池上由麻, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第28回北海道TDM研究会研究発表会(札幌) 2014年11月
  • 2種の血中テイコプラニン濃度測定キット間の測定値の相関性  [通常講演]
    田中寛之, 山田武宏, 戸田貴大, 小林道也, 菅原 満, 猪爪信夫
    第63回日本感染症学会東日本地方会総会学術集会・第61回日本化学療法学会東日本支部総会合同学会(東京) 2014年10月
  • アレルギー性咳嗽治療に用いられる抗アレルギー薬の使用実態~内科と耳鼻咽喉科の比較~  [通常講演]
    石坂 悠, 武隈 洋, 吉村恵理, 吉田憲史, 小嶋希望, 上野英文, 菅原 満
    第24回日本医療薬学会年会(名古屋) 2014年09月
  • UGT1A1 p.P364L変異体およびUGT2B7 p.P366L変異体の光学異性体認識性  [通常講演]
    依田めぐみ, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第28回北海道薬物作用談話会(札幌) 2014年07月
  • 抗ウイルス薬リバビリンのトランスポーターを介した消化管吸収の解析  [通常講演]
    早風郁美, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第28回北海道薬物作用談話会(札幌) 2014年07月
  • 中等量エトポシド (VP-16)/シクロホスファミド (CY)/全身放射線(TBI)前処置レジメンにおけるVP-16のPK/PD解析による投与量の最適化に関する検討  [通常講演]
    田澤佑基, 武隈 洋, 佐藤夕紀, 鷲見正人, 笠師久美子, 井関 健, 菅原 満
    第22回クリニカルファーマシーシンポジウム/医療薬学フォーラム2014(東京) 2014年06月
  • 臨床応用を目指したHPLC-UV法による血中imatinib定量法の確立  [通常講演]
    田中寛之, 木村雄太, 川口啓之, 武隈 洋, 高崎雅彦, 菅原 満
    第31回日本TDM学会・学術大会(東京) 2014年05月
  • 細胞周期変化がエトポシド(VP-16)の殺細胞効果に与える影響  [通常講演]
    田澤佑基, 吉岡美咲, 武隈 洋, 佐藤夕紀, 鷲見正人, 菅原 満
    日本薬学会北海道支部第141回例会(札幌) 2014年05月
  • 実践的医療薬学教育プログラム及びチーム医療・地域医療プログラム~シンポジウム「先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発」  [通常講演]
    菅原 満
    日本薬学会第134年会(熊本) 2014年03月
  • Coenzyme Q10の消化管吸収改善  [通常講演]
    佐藤夕紀, 能登一馬, 竹川悠人, 鷲見正人, 武隈 洋, 菅原 満
    日本コエンザイムQ協会 第11回研究会(東京) 2014年01月
  • 薬物曝露による細胞周期変化が細胞周期依存性の抗癌剤の作用に与える影響  [通常講演]
    吉岡美咲, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第27回北海道TDM研究会研究発表会(札幌) 2013年11月
  • テアニンの体内動態および吸収機構の解明  [通常講演]
    亀田佑生, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第27回北海道TDM研究会研究発表会(札幌) 2013年11月
  • Caco-2細胞におけるNPC1L1を介したコレステロール輸送の特徴  [通常講演]
    阿部沙也華, 竹川悠人, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第27回北海道TDM研究会研究発表会(札幌) 2013年11月
  • 乳剤化による難吸収性物質の吸収改善~コレステロール輸送担体NPC1L1の利用~  [通常講演]
    竹川悠人, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第23回日本医療薬学会年会(仙台) 2013年09月
  • 難吸収性ポリフェノールの乳剤化によるバイオアベイラビリティ改善  [通常講演]
    星山博俊, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第27回北海道薬物作用談話会(江別) 2013年07月
  • Intracellular uptake mechanism of lutein in retinal pigment epithelial cells  [通常講演]
    Sato Y, Kondo Y, Sumi M, Takekuma Y, Sugawara M
    5th World Conference on Drug Absorption, Transport and Delivery (WCDATD)(Uppsala, Sweden) 2013年06月
  • 黄斑色素成分ルテインのヒト網膜上非細胞内への取り込み機構の解明  [通常講演]
    佐藤夕紀, 近藤 有, 武隈 洋, 菅原 満
    日本薬剤学会第28年会(名古屋) 2013年05月
  • hOATPs/rOatpsを介するミコフェノール酸グルクロナイドの輸送特性の種差  [通常講演]
    坂本達彦, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会北海道支部第140例会(札幌) 2013年05月
  • 熱力学的手法を用いた多剤排出輸送担体の基質検索の検討  [通常講演]
    森岡悠紀, 鷲見正人, 佐藤夕紀, 武隈 洋, 菅原 満
    日本薬学会北海道支部第140例会(札幌) 2013年05月
  • Niemann-pick C1 Like-1 (NPC1L1)を介した難吸収性物質の吸収改善へのアプローチ  [通常講演]
    竹川悠人, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会北海道支部第140例会(札幌) 2013年05月
  • より服用しやすい製剤を調製するための工夫  [通常講演]
    菅原 満
    第207回薬剤師臨床セミナー(札幌薬剤師会) 2013年05月 公開講演,セミナー,チュートリアル,講習,講義等 
    札幌薬剤師会誌,68, 53-68 (2013)
  • 一包化調剤時におけるスタチン製剤の保存安定性  [通常講演]
    高地里佳, 石坂 悠, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第133年会(横浜) 2013年03月
  • ヌクレオシドトランスポーターの基質輸送に及ぼすエトポシドの影響  [通常講演]
    高田一輝, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第133年会(横浜) 2013年03月
  • シタラビンの白血球細胞内移行に対するエトポシドの影響  [通常講演]
    高田一輝, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第26回北海道TDM研究会研究発表会(札幌) 2012年12月
  • 一包化調剤時におけるスタチン製剤の保存安定性  [通常講演]
    高地里佳, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第26回北海道薬物作用談話会(札幌) 2012年07月
  • テアニンの脳移行に関与するトランスポーター  [通常講演]
    川守田渉, 亀田佑生, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第26回北海道薬物作用談話会(札幌) 2012年07月
  • 粒子径に着目したCoQ10の乳剤化による吸収改善  [通常講演]
    能登数馬, 佐藤夕紀, 武隈 洋, 菅原 満
    日本薬学会北海道支部第138回例会(札幌) 2012年06月
  • P糖蛋白質(P-gp)発現白血病由来細胞を用いたエトポシド(VP-16)/シクロホスファミド(CY)曝露順序の殺細胞効果に及ぼす影響  [通常講演]
    臼窪一平, 田澤佑基, 佐藤夕紀, 鷲見正人, 柴山良彦, 武隈 洋, 菅原 満
    日本薬学会第132年会(札幌) 2012年03月
  • 国立大学における「実践的医療薬学教育プログラム」の開発  [通常講演]
    中嶋幹郎, 菅原 満, 関根祐子, 小澤光一郎
    日本薬学会第132年会(札幌) 2012年03月
  • Improvement of intestinal absorption of functional foods, lutein and coenzyme Q10  [通常講演]
    Sato Y, Mutoh H, Takekuma Y, Iseki K, Sugawara M
    8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology(Istanbul, Turkey) 2012年03月
  • 中等量VP-16/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンにおけるVP-16のPK/PD解析  [通常講演]
    田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈 洋, 重松明男, 笠師久美子, 山田武宏, 田中淳司, 橋野 聡, 井関 健, 今村雅寛, 菅原 満
    第34回日本造血細胞移植学会総会(大阪) 2012年02月
  • 天然色素成分ルテインの乳化による消化管吸収改善  [通常講演]
    佐藤夕紀, 武隈 洋, 井関 健, 菅原 満
    第9回日本機能性食品医用学会総会(大阪) 2011年12月
  • 機能性食品成分ルテインの乳化による消化管吸収の改善  [通常講演]
    佐藤夕紀, 鈴木里彩, 武隈 洋, 井関 健, 菅原 満
    医療薬学フォーラム2011/第19回クリニカルファーマシーシンポジウム(旭川) 2011年07月
  • オピオイドによる難治性の嘔気とめまいに対しH1受容体拮抗薬とペロスピロンの併用が有効であった症例  [通常講演]
    長田貴之, 柴山良彦, 熊井正貴, 山田武宏, 笠師久美子, 菅原 満, 井関 健
    医療薬学フォーラム2011/第19回クリニカルファーマシーシンポジウム(旭川) 2011年07月
  • 同種造血幹細胞移植時における中等量エトポシド(VP-16)/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンの検討~VP-16のPK/PD解析および培養細胞系を用いたVP-16/CY曝露順序の検討  [通常講演]
    田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈 洋, 重松明男, 笠師久美子, 山田武宏, 井関 健, 今村雅寛, 菅原 満
    第28回日本TDM学会・学術大会(広島) 2011年06月
  • 薬物の消化管吸収~物理化学的性質とトランスポーターを中心に~  [通常講演]
    菅原 満
    日本薬学会北陸支部特別講演(富山) 2011年06月 公開講演,セミナー,チュートリアル,講習,講義等
  • アレルギー疾患治療薬の使用適正化を目指したTDM  [招待講演]
    菅原 満
    第23回日本アレルギー学会春季臨床大会(千葉)(シンポジウム:薬物治療の最適化、招待シンポジスト) 2011年05月
  • 乗り物酔い様の浮遊感を伴うオピオイドの難治性嘔気にペロスピロンが有効であった症例  [通常講演]
    長田貴之, 熊井正貴, 柴山良彦, 山田武宏, 笠師久美子, 菅原 満, 井関 健
    日本薬学会第131年会(静岡) 2011年03月
  • ソラフェニブおよびスニチニブのMRP2(ABCC2)に対する基質特異性  [通常講演]
    柴山良彦, 中野 公, 前田広志, 田口美雪, 池田龍二, 菅原 満, 井関 健, 武田泰生, 山田勝士
    日本薬学会第131年会(静岡) 2011年03月
  • 白血病由来細胞を用いたエトポシド(VP-16)/シクロホスファミド(CY)曝露順序の殺細胞効果への影響  [通常講演]
    田澤佑基, 松村一仙, 笠師久美子, 佐藤夕紀, 鷲見正人, 武隈 洋, 井関 健, 菅原 満
    日本薬学会第131年会(静岡) 2011年03月
  • テアニンの消化管吸収に関与するトランスポーター  [通常講演]
    川守田渉, 堀田雄也, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第131年会(静岡) 2011年03月
  • ルテインの乳化による消化管吸収改善  [通常講演]
    佐藤夕紀, 鈴木里彩, 武隈 洋, 井関 健, 菅原 満
    日本薬学会第131年会(静岡) 2011年03月
  • 国立大学における「実践的医療薬学教育プログラム」の現状  [通常講演]
    小澤光一郎, 菅原 満, 関根祐子, 中嶋幹郎
    日本薬学会第131年会(静岡) 2011年03月
  • マイクロRNA126、210が抗がん薬感受性に及ぼす影響  [通常講演]
    柴山良彦, 田口深雪, 池田龍二, 古川龍彦, 菅原 満, 井関 健, 武田泰生, 山田勝士
    第31回日本臨床薬理学会年会(京都) 2010年12月
  • テアニンの消化管吸収に関与するトランスポーター  [通常講演]
    堀田雄也, 川守田渉, 佐藤夕紀, 鷲見正人, 菅原 満
    日本薬学会北海道支部第135回例会(札幌) 2010年11月
  • 白血病由来細胞を用いたエトポシド(VP-16)/シクロフォスファミド(CY)曝露順序の殺細胞効果への影響  [通常講演]
    田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    第24回北海道TDM研究会研究発表会(札幌) 2010年11月
  • 薬剤師の職能とTDM研究  [招待講演]
    菅原 満
    第49回日本薬学会東北支部大会(福島)(特別講演) 2010年10月
  • 薬剤師業務・研究支援ツールとしてのTDM  [招待講演]
    菅原 満
    第27回日本TDM学会・学術大会(札幌)(教育講演) 2010年06月
  • テアニンの消化管吸収に関与するトランスポーター  [通常講演]
    堀田雄也, 武隈 洋, 菅原 満
    日本薬剤学会第25年会(徳島) 2010年05月
  • 北海道大学薬学部における実務実習事前実習の取り組みとその評価  [通常講演]
    武隈 洋, 小林正紀, 山田勇磨, 板垣史郎, 吉田和幸, 井関 健, 菅原 満
    日本薬学会第130年会(岡山) 2010年03月
  • PK/PD概念に基づいた抗がん剤の分類  [通常講演]
    高橋夏子, 武隈 洋, 小林正紀, 板垣史郎, 菅原 満, 井関 健
    日本薬学会第130年会(岡山) 2010年03月
  • カルベジロールのグルクロン酸抱合に及ぼすエナンチオマー間の相互作用  [通常講演]
    八木澤啓司, 武隈 洋, 菅原 満
    日本薬学会第130年会(岡山) 2010年03月
  • ボリコナゾールの血漿中濃度髄液移行性をモニタリングした脳クリプトコックス症例  [通常講演]
    田島宏恵, 井上直樹, 松村一仙, 武隈 洋, 沖 洋充, 八島萌美, 秋本幸子, 菅原 満, 井関 健
    第23回北海道TDM研究会研究発表会(札幌) 2009年11月
  • 腎移植患者において腎機能の変動がミコフェノール酸体内動態に与える影響  [通常講演]
    大谷 薫, 武隈 洋, 原田幸子, 福澤信之, 下田直彦, 三浦正義, 菅原 満, 野々村克也, 井関 健
    第23回北海道TDM研究会研究発表会(札幌) 2009年11月
  • Heavy water reduced cold hypotoxic injury of cardiomyocytes  [通常講演]
    Fukai M, Yamashita K, Wakayama K, Fukumori D, Haga S, Taniguchi M, Suzuki T, Shimamura T, Ono T, Kinugawa S, Sugawara M, Furukawa H, Ozaki M, Todo S
    American Heart Association 2009 Scientific Session(Orlando, FL) 2009年11月
  • Therapeutic drug monitoring: a useful tool for clinical pharmacists  [通常講演]
    Sugawara M, Iseki K
    2009 China-Japan Pharmacists’ International Forum (CJPIF)( Beijing, China) 2009年11月
  • 北海道大学病院における内服薬疑義照会率の傾向と分析  [通常講演]
    齋藤佳敬, 志賀弘康, 小林正紀, 須田範行, 菅原 満, 井関 健
    第19回日本医療薬学会年会(長崎) 2009年10月
  • 気分障害圏患者の副作用への認知とコンプライアンスへの影響~心理検査との相関性~  [通常講演]
    久保田康生, 木村俊也, 渡邉紀子, 大崎明美, 鈴木克治, 笠師久美子, 菅原 満, 小山 司, 井関 健
    第19回日本医療薬学会年会(長崎) 2009年10月
  • 頭頸部放射線治療において使用される鎮痛薬と腫瘍部位の関連性に関する後ろ向き観察研究  [通常講演]
    長田貴之, 熊井正貴, 山田武宏, 笠師久美子, 鈴木章之, 本間明宏, 福田 諭, 菅原 満, 井関 健
    第3回日本緩和医療薬学会年会(横浜) 2009年10月
  • 北海道TDM研究会の活動を通した地域の薬剤師支援  [招待講演]
    菅原 満
    第35回日本医療薬学公開シンポジウム(金沢)(基調講演) 2009年10月
  • 特別講演:トランスポーターの機能と薬物動態  [通常講演]
    菅原 満
    北海道医療大学ハイテクリサーチセンター整備事業研究報告会(北海道医療大学(当別)) 2009年07月 公開講演,セミナー,チュートリアル,講習,講義等
  • ミコフェノール酸モフェチルの大量投与によっても目標AUCに到達しなかった小児生体移植患者の1症例  [通常講演]
    大谷 薫, 武隈 洋, 原田幸子, 下田直彦, 三浦正義, 菅原 満, 野々村克也, 井関 健
    第26回日本TDM学会・学術大会(新潟) 2009年06月
  • テイコプラニンのローディングドーズがもたらす血中トラフ濃度と有効性の検討-第2次研究中間報告-  [通常講演]
    野田久美子, 田中寛之, 山澤裕司, 齋藤嘉津彦, 小林道也, 菅原 満, 唯野貢司
    第26回日本TDM学会・学術大会(新潟) 2009年06月
  • テイコプラニン初期投与設計への薬剤師介入の効果  [通常講演]
    李 暁光, 武隈 洋, 山崎浩二郎, 西村あや子, 菅原 満, 井関 健
    第26回日本TDM学会・学術大会(新潟) 2009年06月
  • 抗MRSA薬リネゾリドとバンコマイシンの脊椎組織移行性の違い  [通常講演]
    武隈 洋, 加藤貴志, 漆畑英樹, 小松 幹, 高畑雅彦, 菅原 満, 三浪明男, 井関 健
    第26回日本TDM学会・学術大会(新潟) 2009年06月
  • Re-evaluation of heavy water for organ preservation solution; In Vitro study  [通常講演]
    Fukai M, Yamashita K, Wakayama K, Fukumori D, Goto R, Haga S, Hirokata G, Nakakimura S, Sugawara M, Kamachi H, Suzuki T, Shimamura T, Furukawa H, Matsushita M, Ozaki M, Todo S
    American Transplant Congress 2009(Boston, MA) 2009年05月
  • 経口製剤の吸収性評価~物理化学的性質と生理的要因の影響~  [招待講演]
    菅原 満
    第64回医薬品相互作用研究会シンポジウム(弘前)(特別講演) 2009年05月
  • テアニンの消化管吸収に関与するトランスポーター  [通常講演]
    堀田雄也, 武隈 洋, 菅原 満
    日本薬学会北海道支部第132回例会(札幌) 2009年05月
  • 難水溶性薬物の乳剤化とその消化管吸収性に及ぼす胆汁の影響  [通常講演]
    武藤花見, 今井智子, 中山淳司, 鈴木美香, 武隈 洋, 井関 健, 菅原 満
    日本薬学会北海道支部第132回例会(札幌) 2009年05月
  • Na+/モノカルボン酸共輸送担体(SMCT1)の基質認識機構における構造活性相関  [通常講演]
    宮内正二, 駄馬崎泰洋, 菅原 満, Elangovan Gopal, Vadivel Ganapathy
    第129回日本薬学会年会(京都) 2009年03月
  • 造血幹細胞移植における栄養指標と口内症状の評価-第2報-  [通常講演]
    笠師久美子, 柏崎晴彦, 阿部貴恵, 重松明男, 池田陽子, 上野あさひ, 菅原 満, 井関 健
    第24回日本静脈経腸栄養学会(鹿児島) 2009年01月
  • 高カルシウム血症合併食道癌患者において相対的テタニー様症状が疑われた1症例  [通常講演]
    沖 洋充, 齋藤佳敬, 笠師久美子, 菅原 満, 井関 健
    第13回札幌病院薬剤師会会員発表会(札幌) 2008年11月
  • Carvedilolのグルクロン酸抱合に及ぼすエナンチオマー間の相互阻害作用  [通常講演]
    八木澤啓司, 井幡圭佑, 武隈 洋, 菅原 満
    第23回日本薬物動態学会年会(熊本) 2008年10月
  • 当院における緩和ケアチームの活動報告  [通常講演]
    熊井正貴, 田巻知宏, 笠師久美子, 菅原 満, 井関 健
    第2回日本緩和医療薬学会年会(横浜) 2008年10月
  • 消化管吸収予測システムを用いた後発医薬品の薬剤学的同等性評価(2)  [通常講演]
    渡辺祐子, 山本千秋, 下山哲哉, 小林正紀, 板垣史郎, 菅原 満, 平野 剛, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • 消化管吸収予測システムを用いた後発医薬品の薬剤学的同等性評価(1)  [通常講演]
    下山哲哉, 渡辺祐子, 山本千秋, 小林正紀, 板垣史郎, 菅原 満, 平野 剛, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • 頭頸部癌に対するシスプラチン超選択動注における副作用調査  [通常講演]
    熊井正貴, 浅野順次, 笠師久美子, 菅原 満, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • 高齢透析患者の栄養管理におけるNST薬剤師のあり方  [通常講演]
    清川真美, 上野あさひ, 池田陽子, 須田範行, 渡邊昌也, 石川康暢, 菅原 満, 武田宏司, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • マイクロエマルジョン型シクロスポリン製剤の先発医薬品と後発医薬品の製剤学的な比較  [通常講演]
    植田孝介, 武隈 洋, 沖 洋充, 須田範行, 菅原 満, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • がん化学療法における口内炎の予防に対する抗酸化物質の応用がん化学療法における口内炎の予防に対する抗酸化物質の応用  [通常講演]
    鷹野瑠美, 平野 剛, 中田千絵, 笠師久美子, 菅原 満, 小林正紀, 板垣史郎, 井関 健, 大江利治
    第18回日本医療薬学会年会(札幌) 2008年09月
  • リネゾリドの使用状況調査および有効性、副作用に関する調査  [通常講演]
    山崎浩二郎, 西村あや子, 宮本剛典, 武隈 洋, 菅原 満, 井関 健
    第18回日本医療薬学会年会(札幌) 2008年09月
  • FDG-PET検査における薬剤の影響~院内ガイドライン作成の試み~  [通常講演]
    新里利香, 笠師久美子, 鐘ヶ江香久子, 菅原 満, 井関 健
    医療薬学フォーラム2008-第16回クリニカルファーマシーシンポジウム-(東京) 2008年07月
  • 抗MRSA薬テイコプラニンの初期投与量設計による適正使用への関わり  [通常講演]
    木村俊也, 山崎浩二郎, 西村あや子, 坪内孝敏, 横田亜季, 小笠原貴子, 大崎由美子, 執行聡美, 清川真美, 宮本剛典, 武隈 洋, 菅原 満, 井関 健
    日本TDM学会(東京) 2008年06月
  • BCSクラス4に属する薬物の乳剤化とその消化管吸収性に及ぼす胆汁の影響  [通常講演]
    武藤花見, 鈴木美香, 武隈 洋, 井関 健, 菅原 満
    日本薬剤学会第23年会(札幌) 2008年05月
  • 処方せん発行時の抗MRSA薬初期投与設計による医師への情報提供の有用性  [通常講演]
    木村俊也, 山崎浩二郎, 西村あや子, 横田亜季, 小笠原貴子, 大崎由美子, 執行聡美, 清川真美, 宮本剛典, 菅原 満, 井関 健
    第55回北海道薬学大会(札幌) 2008年05月
  • 汎用データベースソフトを用いた持参薬鑑別システムの構築と業務の効率化  [通常講演]
    大崎由美子, 熊井正貴, 川岸 亨, 笠師久美子, 深井敏隆, 菅原 満, 井関 健
    第55回北海道薬学大会(札幌) 2008年05月
  • 汎用データベースソフトを用いた持参薬鑑別システムの構築と運用  [通常講演]
    川岸 亨, 熊井正貴, 齋藤京之, 笠師久美子, 菅原 満, 井関 健
    日本薬学会第128年会(横浜) 2008年03月
  • 北大病院における内服薬疑義照会率の傾向と分析  [通常講演]
    齋藤佳敬, 榊原則寛, 志賀弘康, 沖 洋充, 小林正紀, 川合真次, 深井敏隆, 菅原 満, 井関 健
    日本薬学会第128年会(横浜) 2008年03月
  • 化膿性脊椎炎に対するリネゾリドの臨床効果と脊椎への移行性  [通常講演]
    加藤貴志, 菅原 満, 井関 健, 武隈 洋, 高畑雅彦, 小松 幹, 伊東 学, 三浪明男
    日本薬学会第128年会(横浜) 2008年03月
  • 心臓血管造影剤による急性腎機能低下に対するアセチルシステインの予防効果および製剤の評価  [通常講演]
    清川真美, 澤口利香, 須田範行, 武隈 洋, 菅原 満, 相馬孝光, 川嶋 望, 筒井裕之, 井関 健
    第72回日本循環器学会総会・学術集会(福岡) 2008年03月
  • 医療安全について薬剤師に望むこと~薬剤師の立場から~  [通常講演]
    菅原 満
    室蘭病院薬剤師会研修会 2008年02月 公開講演,セミナー,チュートリアル,講習,講義等
  • 小腸ろう周囲にびらんを呈した短腸症候群患者への栄養管理の一例  [通常講演]
    植田孝介, 久保ちづる, 林みゆき, 須田範行, 菅原 満, 井関 健, 七戸俊明, 武田宏司
    第23回日本静脈経腸栄養学会(京都) 2008年02月
  • 造血幹細胞移植における栄養指標と口内症状の評価  [通常講演]
    笠師久美子, 柏崎晴彦, 阿部貴恵, 須田範行, 菅原 満, 井関 健
    第23回日本静脈経腸栄養学会(京都) 2008年02月
  • Intestinal absorption of emulsified preparation of drugs belong to BCS class 4  [通常講演]
    Sugawara M, Mutoh H, Suzuki M, Takekuma Y, Iseki K
    2008 AAPS Annual Meeting(Atlanta, GA) 2008年
  • リネゾリドの椎間板への移行性  [通常講演]
    加藤貴志, 菅原 満, 井関 健, 武隈 洋, 高畑雅彦, 小松 幹, 伊藤 学, 三浪明男
    第21回北海道TDM研究会研究発表会(札幌) 2007年12月
  • 腎機能低下時における抗MRSA薬、抗ウイルス薬のTDM  [通常講演]
    菅原 満
    ファルモミエ・三重県病院薬剤師会研修会(津) 2007年10月 公開講演,セミナー,チュートリアル,講習,講義等
  • Coenzyme Q10の消化管吸収挙動:排出系トランスポーターの関与  [通常講演]
    落合彰子, 小林正紀, 板垣史郎, 平野 剛, 菅原 満, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • オピオイド製剤の適正使用に関する調査  [通常講演]
    斎藤由起子, 沖 洋充, 平野 剛, 菅原 満, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • 全身性エリトマトーデス(SLE)患者に対するミコフェノール酸モフェチル(MMF)の適用とTDMの有用性  [通常講演]
    武隈 洋, 奥 健志, 小笠原貴子, 山﨑浩二郎, 菅原 満, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • テイコプラニン(TEIC)TDM実施患者における血中濃度と疾患別臨床評価  [通常講演]
    西村あや子, 坪内孝敏, 山﨑浩二郎, 宮本剛典, 武隈 洋, 菅原 満, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • 栄養療法における脂肪乳剤の使用に関する意識調査および適正使用の推進  [通常講演]
    鷹野瑠美, 須田範行, 平野 剛, 笠師久美子, 菅原 満, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • 処方オーダによる後発医薬品への変更許可システムとその稼働状況  [通常講演]
    川合真次, 深井敏隆, 荻野 修, 菅原 満, 櫻井恒太郎, 井関 健
    第17回日本医療薬学会年会(前橋) 2007年09月
  • テイコプラニンのローディングドーズがもたらす血中トラフ濃度と有効性の検討-中間報告-  [通常講演]
    田中寛之, 山澤裕司, 齋藤嘉津彦, 小林道也, 菅原 満, 唯野貢司
    第24回日本TDM学会学術大会(金沢) 2007年07月
  • 地域の中でのチーム医療:北海道TDM研究会の活動を通じて  [招待講演]
    菅原 満, 唯野貢司
    第24回日本TDM学会学術大会(金沢)(シンポジウム:チーム医療に貢献するTDMの実際 招待) 2007年07月
  • ゲフィチニブ導入時における薬剤師の役割  [通常講演]
    沖 洋充, 細貝久美子, 久保田康生, 菅原 満, 井関 健
    第10回日本医薬品情報学会学術大会(札幌) 2007年07月
  • 院内LANを用いた情報提供、添付文書閲覧システムの使用状況  [通常講演]
    川合真次, 川岸 亨, 住吉一宏, 深井敏隆, 荻野 修, 菅原 満, 櫻井恒太郎, 井関 健
    第10回日本医薬品情報学会学術大会(札幌) 2007年07月
  • 北大病院における持参薬確認業務への取り組み  [通常講演]
    齋藤京之, 熊井正貴, 小田島澄子, 海藤文恵, 鳥飼真之介, 執行聡美, 川岸諭佳, 沖 洋充, 深井敏隆, 荻野 修, 菅原 満, 井関 健
    第54回北海道薬学大会(札幌) 2007年05月
  • ビスホスホネート製剤ゾメタの使用状況調査  [通常講演]
    上野英文, 寺林久幸, 澤口利香, 久保田康生, 須田範行, 沖 洋充, 笠師久美子, 菅原 満, 井関 健
    第54回北海道薬学大会(札幌) 2007年05月
  • 医薬品の消化管からの吸収~物理化学的性質とトランスポーターを中心に~  [通常講演]
    菅原 満
    平成18年度北海道薬剤師会生涯研修会(稚内) 2007年03月 公開講演,セミナー,チュートリアル,講習,講義等
  • 医薬品の消化管からの吸収~物理化学的性質とトランスポーターを中心に~  [通常講演]
    菅原 満
    平成18年度北海道薬剤師会生涯研修会(日高) 2007年03月 公開講演,セミナー,チュートリアル,講習,講義等
  • ラットおよびヒト間のMPA(ミコフェノール酸)体内動態の違いにおけるMRP2(multidrug resistance-associated protein 2)及びOAT(organic anion transporter)の関与  [通常講演]
    垣内 悠, 武隈 洋, 山﨑浩二郎, 井関 健, 菅原 満
    日本薬学会第127年会(富山) 2007年03月
  • 日本人におけるα1-酸性糖蛋白質(オロソムコイド)遺伝子多型の発現頻度解析  [通常講演]
    長田貴之, 武隈 洋, 山﨑浩二郎, 井関 健, 菅原 満
    日本薬学会第127年会(富山) 2007年03月
  • カルベジロールのグルクロン酸抱合能に与えるUGT1A1(G71R)、2B7(A71S, H268Y)バリアントの影響  [通常講演]
    武中 徹, 武隈 洋, 清川真美, 山﨑浩二郎, 岡本 洋, 北畠 顕, 筒井裕之, 井関 健, 菅原 満
    日本薬学会第127年会(富山) 2007年03月
  • タクロリムス(TAC)併用腎移植患者におけるミコフェノール酸(MPA)の血中濃度変動要因解析  [通常講演]
    武隈 洋, 寺岡栄美, 澤口利香, 山﨑浩二郎, 森田 研, 下田直彦, 堀田記世彦, 岩見大基, 渡井至彦, 菅原 満, 野々村克也, 井関 健
    第40回日本臨床腎移植学会(石川) 2007年02月
  • Contribution of concentrative nucleoside transporter 3 (CNT3) in intestinal absorption of ribavirin  [通常講演]
    Sugawara M, Kuniki K, Yamamoto T, Takekuma Y
    2007 AAPS Annual Meeting(San Diego, CA) 2007年
  • 医薬品の消化管からの吸収~物理化学的性質とトランスポーターを中心に~  [通常講演]
    菅原 満
    平成18年度北海道薬剤師会生涯研修会(旭川) 2006年12月 公開講演,セミナー,チュートリアル,講習,講義等
  • 薬物療法時の血液浄化療法の影響~リネゾリド・ガンシクロビルについて~  [通常講演]
    武隈 洋, 山﨑浩二郎, 宮本 剛, 菅原 満, 井関 健
    第20回北海道TDM研究会研究発表会(札幌) 2006年11月
  • ヒトNa+/モノカルボン酸共輸送担体(hSMCT)の基質特異性  [通常講演]
    宮内正二, 佐々木塁, 板垣史郎, 井関 健, 菅原 満, 菊川峰志, Vadivel Ganapathy, 加茂直樹
    第21回日本薬物動態学会年会(東京) 2006年11月
  • リバビリン取り込みにおけるヌクレオシドトランスポーターCNTおよびENTの輸送活性の関連性  [通常講演]
    山本 崇, 武隈 洋, 平野 剛, 井関 健, 宮内正二, 菊川峰志, 加茂直樹, 菅原 満
    第21回日本薬物動態学会年会(東京) 2006年11月
  • アセチルシステイン院内製剤の調製と造影剤腎症に対する予防効果  [通常講演]
    清川真美, 澤口利香, 須田範行, 菅原 満, 井関 健, 武隈 洋, 石森直樹, 相馬孝光, 川嶋 望, 筒井裕之
    第71回北海道シネアンジオ研究会(札幌) 2006年11月
  • スルバクタム/セフォペラゾン製剤の後発医薬品導入に際する有効性の比較検討  [通常講演]
    大西 潤, 井藤達也, 志賀隆博, 高木智史, 鈴木 岳, 武隈 洋, 菅原 満, 竹本 功, 井関 健
    第16回日本医療薬学会年会(金沢) 2006年09月
  • テイコプラニン投与時における至適ローディングドーズの検討~新旧TDM解析支援ソフトウェア間の有用性の比較~  [通常講演]
    小笠原貴子, 武隈 洋, 山﨑浩二郎, 沖 洋充, 菅原 満, 井関 健
    第16回日本医療薬学会年会(金沢) 2006年09月
  • ポリアクリル酸ナトリウム(PANA)人工唾液の使用動向とその評価  [通常講演]
    笠師久美子, 須田範行, 鄭 漢忠, 菅原 満, 井関 健
    第16回日本医療薬学会年会(金沢) 2006年09月
  • コエンザイムQ10の消化管吸収挙動:製剤的工夫による違い  [通常講演]
    井関 健, 落合彰子, 黒川俊光, 板垣史郎, 平野 剛, 菅原 満
    第16回日本医療薬学会年会(金沢) 2006年09月
  • 外来化学療法における服薬指導充実のための病棟-外来間連携ツールの構築  [通常講演]
    久保田康生, 中里恭子, 須田範行, 沖 洋充, 菅原 満, 小林道也, 齊藤浩司, 井関 健
    第16回日本医療薬学会年会(金沢) 2006年09月
  • 心臓血管造影剤による急性腎機能低下に対するアセチルシステインの予防効果および製剤の評価  [通常講演]
    清川真美, 澤口利香, 須田範行, 菅原 満, 井関 健
    第16回日本医療薬学会年会(金沢) 2006年09月
  • 中性アミノ酸トランスポーターSNAT2の発現変動  [通常講演]
    柏木 仁, 山﨑浩二郎, 武隈 洋, 井関 健, 菅原 満
    第20回北海道薬物作用談話会(札幌) 2006年07月
  • 高度腎機能障害患者におけるリネゾリドの体内動態の変動  [通常講演]
    山﨑浩二郎, 宮本剛典, 菅原 満, 井関 健, 武隈 洋, 太田薫子, 伊藤洋子, 南須原康行, 西村正治
    医療薬学フォーラム2006/第14回クリニカルファーマシーシンポジウム(大阪) 2006年07月
  • 血清アルブミンを中心としたMPA血中濃度の変動要因解析  [通常講演]
    寺岡栄美, 山﨑浩二郎, 菅原 満, 井関 健, 武隈 洋, 森田 研, 下田直彦, 堀田記世彦, 岩見大基, 野々村克也, 渡井至彦
    第24回北海道腎移植談話会(札幌) 2006年07月
  • 副作用症状を来した肝移植患者に対する免疫抑制剤の選択  [通常講演]
    小笠原貴子, 新沼朋美, 沖 洋充, 武隈 洋, 深井敏隆, 荻野 修, 菅原 満, 井関 健
    第53回北海道薬学大会(札幌) 2006年05月
  • 注射オーダを利用した特定生物由来製剤の使用管理システム  [通常講演]
    川合真次, 山﨑浩二郎, 宮本剛典, 荻野 修, 菅原 満, 井関 健, 櫻井恒太郎
    日本薬学会第126年会(仙台) 2006年03月
  • ヌクレオシドトランスポーターを介した抗ウイルス薬リバビリンの消化管吸収  [通常講演]
    國木賢一, 山本 崇, 武隈 洋, 菅原 満, 井関 健
    日本薬剤学会第21年会(金沢) 2006年03月
  • カルベジロールの体内動態変動に及ぼすグルクロン酸転位酵素およびCYP2D6遺伝子多型の影響  [通常講演]
    武中 徹, 武隈 洋, 清川真美, 山﨑浩二郎, 菅原 満, 宮崎勝巳, 岡本 洋, 北畠 顯, 筒井裕之
    第19回北海道TDM研究会研究発表会(札幌) 2005年11月
  • 造影剤による腎機能低下の予防を目的としたアセチルシステインゼリーの調製と評価  [通常講演]
    須田範行, 澤口利香, 清川真美, 菅原 満, 井関 健
    第18回北海道製剤研究会(札幌) 2005年11月
  • 健康食品に対する意識と摂取状況およびそのデータベース(DB)化  [通常講演]
    久保田康生, 沖 洋充, 菅原 満, 山崎浩一, 西村正治
    第15回日本医療薬学会年会(岡山) 2005年10月
  • 院内LANを用いた情報提供、添付文書閲覧システムの構築  [通常講演]
    川岸 亨, 橋本純一, 住吉一宏, 川合真次, 深井敏隆, 荻野 修, 菅原 満, 櫻井恒太郎, 宮崎勝巳
    第15回日本医療薬学会年会(岡山) 2005年10月
  • 救急・集中治療室12例におけるフレカイニド静注薬の効果解析  [通常講演]
    松田直之, 大城あき子, 下嶋秀和, 久保田信彦, 星野弘勝, 早川峰司, 澤村 淳, 石川岳彦, 丸藤 哲, 武隈 洋, 菅原 満
    第6回抗不整脈薬TDM研究会(東京) 2005年
  • 神経因性疼痛に対する酢酸フレカイニドの鎮痛効果の検討  [通常講演]
    武隈 洋, 山﨑浩二郎, 志賀弘康, 菅原 満, 宮崎勝巳, 小澤剛久, 柴田万里子, 橋本聡一, 森本裕二
    第6回抗不整脈薬TDM研究会(東京) 2005年
  • 腎移植患者におけるタクロリムス併用時の少数採血点によるミコフェノール酸AUC0-12推定  [通常講演]
    寺岡栄美, 武隈 洋, 山﨑浩二郎, 高田陽美, 菅原 満, 渡井至彦, 森田 研, 福澤信之, 野々村克也, 宮崎勝巳
    第22回日本TDM学会学術大会(沖縄) 2005年
  • カルベジロールの体内動態に及ぼすグルクロン酸転位酵素およびCYP2D6遺伝子多型の影響  [通常講演]
    武隈 洋, 武中 徹, 清川真美, 山﨑浩二郎, 岡本 洋, 菅原 満, 北畠 顯, 筒井裕之, 宮崎勝巳
    第22回日本TDM学会学術大会(沖縄) 2005年
  • 薬物のα1-酸性糖タンパク質への結合と臨床  [招待講演]
    菅原 満
    第22回日本TDM学会学術大会(沖縄) 2005年 公開講演,セミナー,チュートリアル,講習,講義等
  • ヌクレオシドトランスポーターを介した抗ウイルス薬リバビリンの消化管吸収  [通常講演]
    國木賢一, 山本 崇, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道部第124回例会(札幌) 2005年
  • 当院における外来治療センターの現状と問題点  [通常講演]
    須田範行, 瀬戸恵介, 熊井正貴, 岩井美和子, 志賀弘康, 宮本剛典, 荻野 修, 菅原 満, 宮崎勝巳
    日本薬学会第125年会(東京) 2005年
  • 心疾患患者におけるカルベジロール薬物動態の母集団パラメータ解析  [通常講演]
    武隈 洋, 清川真美, 武中 徹, 山﨑浩二郎, 岡本 洋, 菅原 満, 北畠 顕, 筒井裕之, 宮崎勝巳
    日本薬学会第125年会(東京) 2005年
  • ヌクレオシドトランスポーターを介した薬物輸送~CNTとENTの比較~  [通常講演]
    山本 崇, 國木賢一, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会第125年会(東京) 2005年
  • Limited sampling strategy for therapeutic drug monitoring of mycophenolic acid after renal transplantation  [通常講演]
    Watarai Y, Morita K, Fukuzawa N, Nonomura K, Takekuma Y, Yamazaki K, Takada H, Sugawara M, Miyazaki K
    American Society of Transplant Surgeons, American Society of Transplantation 6th Annual Conference(Seattle, WA) 2004年
  • Functional identity of SLC5A8 as a sodium-coupled transporter for short-chain fatty acids  [通常講演]
    Prasad P. D, Sugawara M, Fei Y.-J, Gopal E, Miyauchi S, Ganapathy V
    Pharmaceutical Sciences World Congress(Kyoto) 2004年
  • Inhibitory effects of basic drugs on the sodium-dependent transport of L-alanine via system B0 in the small intestine  [通常講演]
    Sugawara M, Kitakubo M, Takekuma Y, Ganapathy V, Miyazaki K
    Pharmaceutical Sciences World Congress(Kyoto) 2004年
  • Transport of ribavirin via nucleoside transporters in the trophoblast  [通常講演]
    Morita T, Takekuma Y, Sugawara M, Miyazaki K
    Pharmaceutical Sciences World Congress(Kyoto) 2004年
  • QOL向上を目指した院内固形製剤の調製  [招待講演]
    菅原 満
    日本薬剤学会創立20周年記念大会(東京) 2004年
  • 神経因性疼痛に対する酢酸フレカイニドの鎮痛効果とTDMの有用性  [通常講演]
    山﨑浩二郎, 武隈 洋, 志賀弘康, 菅原 満, 宮崎勝巳, 小澤剛久, 柴田万里子, 橋本総一, 森本裕二
    第18回北海道TDM研究会研究発表会(札幌) 2004年
  • 癌化学療法時の口内炎予防を目的としたメシル酸カモスタット口腔内崩壊錠の調製とその評価  [通常講演]
    須田範行, 今野安大, 中田 宏, 菅原 満, 宮崎正三, 宮崎勝巳
    第17回北海道製剤研究会(札幌) 2004年
  • Reguratory mechanism of ATA2 (SNAT2), an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock, and amino acid deprivation  [通常講演]
    Kashiwagi H, Sugawara M, Takekuma Y, Ganapathy V, Miyazaki K
    第19回日本薬物動態学会年会(金沢) 2004年
  • Structure-affinity relationship in the interactions of human organic anion transporter 1 with nucleic acids and their analogs  [通常講演]
    Oda M, Mochizuki T, Takekuma Y, Sugawara M, Miyazaki K
    第19回日本薬物動態学会年会(金沢) 2004年
  • 麻薬オーダリングシステムの構築とその運用  [通常講演]
    志賀弘康, 川合真次, 荻野 修, 菅原 満, 宮崎勝巳
    第14回日本医療薬学会年会(千葉) 2004年
  • 造影剤による腎機能低下の予防を目的としたアセチルシステインゼリーの調製と評価  [通常講演]
    須田範行, 新里利香, 清川真美, 金内美妃, 菅原 満, 郡 修徳, 宮崎勝巳
    第14回日本医療薬学会年会(千葉) 2004年
  • 北海道大学病院における治験実施体制の整備と新たな取り組み  [通常講演]
    後藤瑞子, 橋本あきら, 荻野 修, 菅原 満, 宮崎勝巳, 亀田悦子, 奥原芳子, 河野敏春, 佐藤典宏, 遠藤 晃, 櫻井恒太郎, 小池隆夫
    第25回日本臨床薬理学会年会(静岡) 2004年
  • 癌化学療法におけるリスクマネジメントへの取り組み-癌化学療法データベースの構築と運用-  [通常講演]
    熊井正貴, 武隈 洋, 沖 祥充, 久保田康生, 川岸 亨, 松浦麻耶, 宮本剛典, 荻野 修, 菅原 満, 宮崎勝巳
    医療薬学フォーラム2004/第12回クリニカルファーマシーシンポジウム(札幌) 2004年
  • 肺癌患者への化学療法に対する薬剤管理指導業務(2)-ワークシートの活用とデータベース化-  [通常講演]
    久保田康生, 吉田美那子, 沖 洋充, 菅原 満, 宮崎勝巳
    医療薬学フォーラム2004/第12回クリニカルファーマシーシンポジウム(札幌) 2004年
  • 肺癌患者への化学療法に対する薬剤管理指導業務(1)-副作用説明書の作成と活用-  [通常講演]
    沖 洋充, 吉田美那子, 久保田康生, 菅原 満, 宮崎勝巳
    医療薬学フォーラム2004/第12回クリニカルファーマシーシンポジウム(札幌) 2004年
  • カルベジロール血漿中濃度に及ぼすグルクロン酸抱合能の影響  [通常講演]
    武隈 洋, 清川真美, 山﨑浩二郎, 米澤一也, 岡本 洋, 菅原 満, 北畠 顯, 宮崎勝巳
    第21回日本TDM学会・学術大会(大阪) 2004年
  • 急性腎不全患者におけるフレカイニドの血中濃度と頻脈抑制作用の一例  [通常講演]
    松田直之, 平安山直美, 早川峰司, 澤村 淳, 亀山 隆, 丸藤 哲, 武隈 洋, 菅原 満, 宮崎勝巳
    第5回抗不整脈薬TDM研究会(福岡) 2004年
  • 麻薬オーダリングシステムの構築とその運用  [通常講演]
    志賀弘康, 川合真次, 荻野 修, 菅原 満, 宮崎勝巳
    第51回北海道薬学大会(札幌) 2004年
  • hOAT1の基質認識における構造相関~核酸類似構造化合物を用いた検討~  [通常講演]
    小田真也, 望月敬浩, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第122回例会(札幌) 2004年
  • AAG variantに対するクロルプロマジンの結合に及ぼすシアル酸の影響  [通常講演]
    中川 勉, 佐々木花, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会第124年会(大阪) 2004年
  • hOAT1を介した有機アニオン輸送に対するキサンチン系薬物の阻害効果  [通常講演]
    菅原 満, 望月敬浩, 武隈 洋, 宮崎勝巳
    日本薬学会第124年会(大阪) 2004年
  • PSP取り込み過程における有機アニオントランスポーターの寄与  [通常講演]
    板垣史郎, 菅原 満, 小林道也, 平野 剛, 宮崎勝巳, 井関 健
    日本薬学会第124年会(大阪) 2004年
  • タキソール注投与時の結晶析出に関する報告  [通常講演]
    岩井美和子, 須田範行, 菅原 満, 宮崎勝巳
    日本薬学会第124年会(大阪) 2004年
  • 肝のう胞治療時のジソピラミド血中濃度モニタリング-エタノール注入療法患者の症例-  [通常講演]
    坪井 瞳, 板垣まゆ子, 今田愛也, 金重啓子, 樟本賢首, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会第124年会(大阪) 2004年
  • 癌化学療法の調剤業務支援のためのプロトコールデータベースの構築と運用  [通常講演]
    武隈 洋, 岩井美和子, 藤原俊恵, 川岸 亨, 熊井正貴, 松浦麻耶, 前佛美也子, 高橋悠子, 相楽賢一, 馬渕朋美, 須田範行, 宮本剛典, 荻野 修, 菅原 満, 宮崎勝巳
    日本薬学会第124年会(大阪) 2004年
  • 外国人Pharm.D.の指摘による循環器科  [通常講演]
    沖 洋充, 榊原則寛, 菅原 満, 宮崎勝巳
    精神科における服薬指導の拡充、日本薬学会第124年会サテライトシンポジウム「厚生労働科学研究費補助金(医薬品等医療技術リスク評価研究事業)研究成果報告会」(名古屋) 2004年
  • hOAT1を介したアニオン輸送に対するキサンチン系薬物の阻害効果  [通常講演]
    望月敬浩, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第121回例会(札幌) 2003年
  • 肝のう胞治療時のジソピラミド血中濃度モニタリング-エタノール注入療法患者の症例-  [通常講演]
    坪井 瞳, 板垣まゆ子, 今田愛也, 阿部康子, 金重啓子, 樟本賢首, 岸野吏志, 菅原 満, 宮崎勝巳
    第17回北海道TDM研究会(札幌) 2003年
  • 薬物吸収予測システムを用いた胃内pH変動に伴う薬物吸収性変化の評価  [通常講演]
    門村将太, 井藤達也, 武隈 洋, 竹本 功, 菅原 満, 宮崎勝巳
    第8回札幌病院薬剤師会会員発表会(札幌) 2003年
  • タキソール注投与時の結晶析出に関する報告  [通常講演]
    岩井美和子, 須田範行, 菅原 満, 宮崎勝巳
    第16回北海道製剤研究会(札幌) 2003年
  • 難治性の外耳および中耳炎に対するブロー液の使用経験  [通常講演]
    須田範行, 柏村正明, 福田 諭, 岩井美和子, 菅原 満, 宮崎勝巳
    第16回北海道製剤研究会(札幌) 2003年
  • Changes in glycosylation of alpha-1-acid-glycoprotein during liver regeneration in the rat  [通常講演]
    Nakagawa T, Kishino S, Sugawara M, Miyazaki K
    第76回日本生化学会大会(横浜) 2003年
  • 抗ウイルス薬リバビリンの胎盤透過機構  [通常講演]
    森田 崇, 武隈 洋, 菅原 満, 宮崎勝巳
    第18回日本薬物動態学会年会(札幌) 2003年
  • 薬物吸収予測システムを用いた経口投与製剤の溶出性・吸収性評価  [通常講演]
    坂本麻美, 武隈 洋, 岸野吏志, 菅原 満, 宮崎勝巳
    第18回日本薬物動態学会年会(札幌) 2003年
  • 薬物吸収予測システムを用いた胃内pH変動に伴う薬物吸収性変化の評価  [通常講演]
    門村将太, 武隈 洋, 竹本 功, 菅原 満, 宮崎勝巳
    第18回日本薬物動態学会年会(札幌) 2003年
  • α1-酸性糖蛋白質不均一性体の立体選択的薬物結合における糖鎖構造の影響  [通常講演]
    中川 勉, 岸野吏志, 菅原 満, 宮崎勝巳
    第18回日本薬物動態学会年会(札幌) 2003年
  • 循環器病棟においてTDMを有効利用した症例  [通常講演]
    清川真美, 武隈 洋, 岸野吏志, 深井敏隆, 高木眞弓, 米澤一也, 菅原 満, 宮崎勝巳, 北畠 顯
    第13回日本医療薬学会年会(神戸) 2003年
  • 生体部分肝移植患者におけるMicafungin(「Fungard®」)の体内動態  [通常講演]
    岸野吏志, 馬渕朋美, 菅原 満, 嶋村 剛, 古川博之, 藤堂 省, 宮崎勝巳
    第20回日本TDM学会学術大会(横浜) 2003年
  • 生体肝移植患者におけるタクロリムスの体内動態とその変動要因  [通常講演]
    岸野吏志, 菅原 満, 古川博之, 藤堂 省, 宮崎勝巳
    第109回日本外科学会定期学術集会(札幌) 2003年
  • 生体肝移植患者におけるタクロリムスの体内動態とその変動要因  [通常講演]
    岸野吏志, 菅原 満, 宮崎勝巳, 古川博之, 藤堂 省
    第11回肝臓病態生理研究会(福岡) 2003年
  • フェンタニルパッチ連日投与により傾眠が改善できた一症例  [通常講演]
    志賀弘康, 荻野 修, 菅原 満, 宮崎勝巳
    第50回北海道薬学大会(札幌) 2003年
  • カルニチントランスポーター(OCTN2)発現細胞を用いた基質認識特性の解明  [通常講演]
    高野太樹, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第120回例会(札幌) 2003年
  • システムAアミノ酸トランスポーターの活性・発現におよぼすインスリンの影響  [通常講演]
    柏木 仁, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第120回例会(札幌) 2003年
  • 抗ウイルス薬リバビリンの胎盤透過機構  [通常講演]
    森田 崇, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第120回例会(札幌) 2003年
  • 消化管内の生理的条件を考慮した薬物吸収評価系の構築〜プロドラッグの吸収評価〜  [通常講演]
    何 新, 武隈 洋, 菅原 満, 宮崎勝巳
    日本薬学会第123年会(長崎) 2003年
  • 癌化学療法時の口内炎予防を目的としたメシル酸カモスタット口腔内速崩錠の調製とその評価  [通常講演]
    須田範行, 今野安大, 岩井美和子, 森田 豊, 中田 宏, 菅原 満, 宮崎正三, 宮崎勝巳
    日本薬学会第123年会(長崎) 2003年
  • α1-酸性糖蛋白質への立体選択的な薬物結合におけるシアル酸の影響  [通常講演]
    中川 勉, 伊藤 慎, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会第123年会(長崎) 2003年
  • システムB0を介した中性アミノ酸の輸送におよぼす塩基性薬物の影響  [通常講演]
    北窪真弓, 武隈 洋, 菅原 満, Vadivel ganapathy, 宮崎勝巳
    日本薬学会第123年会(長崎) 2003年
  • 注射薬の無菌調製に関する検討  [通常講演]
    岩井美和子, 須田範行, 菅原 満, 宮崎勝巳
    第15回北海道製剤研究会(札幌) 2002年
  • α1-酸性糖蛋白質の不均一性体と薬物の結合性〜シアル酸の影響〜  [通常講演]
    伊藤 慎, 中川 勉, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第119回例会(札幌) 2002年
  • 消化管内の生理的条件を考慮した薬物吸収評価系の確立  [通常講演]
    何 新, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部第119回例会(札幌) 2002年
  • LECラットにおける有機アニオン化合物の胆汁排泄機構  [通常講演]
    板垣史郎, 菅原 満, 宮崎勝巳
    第17回日本薬物動態学会年会(東京) 2002年
  • 胃内pH変動を想定した薬物吸収予測システムによる製剤からの薬物溶出性・吸収性評価  [通常講演]
    門村将太, 菅原 満, 宮崎勝巳
    第17回日本薬物動態学会年会(東京) 2002年
  • 肝移植患者における内因性cortisolの尿中代謝物を用いた薬物代謝能(CYP3A4)評価法の検討  [通常講演]
    岸野吏志, 小川真紀, 菅原 満, 古川博之, 藤堂 省, 宮崎勝巳
    第12回日本医療薬学会年会(福岡) 2002年
  • より充実した情報提供に向けて−新データシステムの構築−  [通常講演]
    橋本純一, 山下恭範, 榊原則寛, 川合真次, 深井敏隆, 荻野 修, 菅原 満, 宮崎勝巳
    第12回日本医療薬学会年会(福岡) 2002年
  • リスク軽減を目的とした調剤業務のシステム化  [通常講演]
    橋本純一, 深井敏隆, 荻野 修, 菅原 満, 宮崎勝巳
    第49回北海道薬学大会(札幌) 2002年
  • 生体部分肝移植患者におけるLinezolid(「Zyvox®」)の体内動態  [通常講演]
    岸野吏志, 馬渕朋美, 菅原 満, 嶋村 剛, 古川博之, 藤堂 省, 宮崎勝巳
    第19回日本TDM学会学術大会(熊本) 2002年
  • 生体部分肝移植患者におけるSirolimus併用時のTacrolimusの薬物動態  [通常講演]
    馬渕朋美, 宮本剛典, 岸野吏志, 菅原 満, 嶋村 剛, 古川博之, 藤堂 省, 宮崎勝巳
    第19回日本TDM学会学術大会(熊本) 2002年
  • 薬物−生体膜間の静電的相互作用をファクターとした薬物吸収性予測  [招待講演]
    菅原 満
    日本薬学会第122年会(千葉) 2002年
  • α1-酸性糖蛋白質とその不均一性体の糖鎖構造解析  [通常講演]
    中川 勉, 越浪由加, 佐々木花, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • α1-酸性糖蛋白質の不均一性体とPropranolol光学異性体の立体選択的結合性  [通常講演]
    伊藤 慎, 中川 勉, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • 小腸上皮細胞におけるポリアミン取り込み機構  [通常講演]
    瀬戸恵介, 菅原 満, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • 消化管内pH変動および腸管代謝を考慮した薬物吸収予測システムの構築  [通常講演]
    何 新, 菅原 満, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • VRE感染症治療剤ザイボックス錠の粉砕可否に関する検討  [通常講演]
    菅原 満, 荻野 修, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • 肝移植患者におけるCHDF(持続血液濾過透析)施行時のGanciclovirの血中動態  [通常講演]
    岸野吏志, 菅原 満, 宮崎勝巳, 古川裕之, 藤堂 省
    日本薬学会第122年会(千葉) 2002年
  • 薬学部4年生の医薬品情報(DI)実習における修得度のアンケート調査  [通常講演]
    川合真次, 平野 剛, 菅原 満, 井関 健, 岸野吏志, 荻野 修, 野村靖幸, 宮崎勝巳
    日本薬学会第122年会(千葉) 2002年
  • 薬剤師主導による心不全患者に対するカルベジロール投与プロトコールの構築(2)−カルベジロール血中濃度測定が処方構築に有用だった例−  [通常講演]
    清川真美, 岸野吏志, 深井敏隆, 高木眞弓, 米澤一也, 小林道也, 菅原 満, 宮崎勝巳, 北畠 顯
    第15回北海道TDM研究会(札幌) 2001年
  • グルタミントランスポーターの機能解析  [通常講演]
    菅原 満
    創剤フォーラム第7回若手研究会(札幌) 2001年
  • α1-acid flycoproteinのマイクロヘテロジェニティーとpropranolol光学異性体に対する結合性  [通常講演]
    伊藤 慎, 中川 勉, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部例会第117回例会(札幌) 2001年
  • Caco-2細胞におけるPSP排出機構  [通常講演]
    板垣史郎, 菅原 満, 宮崎勝巳
    日本薬学会北海道支部例会第117回例会(札幌) 2001年
  • β−ラクタム系抗生物質の消化管吸収における重炭酸イオンの影響  [通常講演]
    山崎浩二郎, 北窪真弓, 小林道也, 菅原 満, 宮崎勝巳
    第16回日本薬物動態学会年会(神戸) 2001年
  • Caco-2細胞における多剤排出蛋白質を介したPSP輸送  [通常講演]
    板垣史郎, 小林道也, 井関 健, 菅原 満, 宮崎勝巳
    第16回日本薬物動態学会年会(神戸) 2001年
  • 院内製剤1.0M安息香酸ナトリウム注射液、0.25Mフェニル酢酸ナトリウム注射液に関する検討−製剤の安定性および生体肝移植直前の高アンモニア血症に対する使用例−  [通常講演]
    岩井美和子, 武隈 洋, 須田範行, 岸野吏志, 菅原 満, 古川博之, 藤堂 省, 宮崎勝巳
    第11回日本医療薬学会年会(東京) 2001年
  • 薬剤師主導による心不全患者に対するカルベジロール投与プロトコールの構築(2)−カルベジロール血中濃度測定が処方構築に有用だった例−  [通常講演]
    清川真美, 岸野吏志, 深井敏隆, 高木眞弓, 米澤一也, 小林道也, 菅原 満, 宮崎勝巳, 北畠 顯
    第11回日本医療薬学会年会(東京) 2001年
  • 北大病院におけるCRC業務について  [通常講演]
    高田陽美, 橋本あきら, 荻野 修, 菅原 満, 竹内ひとみ, 奥原芳子, 宮崎勝巳, 小柳知彦
    第48回北海道薬学大会(札幌) 2001年
  • 当院薬剤部におけるリスク回避のための対策  [通常講演]
    久保田康生, 深井敏隆, 荻野 修, 菅原 満, 宮崎勝巳
    第48回北海道薬学大会(札幌) 2001年
  • 院内製剤の安定性と使用期限に関する検討  [通常講演]
    岩井美和子, 志賀弘康, 山下恭範, 須田範行, 武隈 洋, 岸野吏志, 菅原 満, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • 肝移植患者におけるタクロリムスの体内動態(2)  [通常講演]
    岸野吏志, 志賀弘康, 山下恭範, 岩井美和子, 菅原 満, 古川博之, 藤堂 省, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • 病棟業務における薬剤師の職能−循環器科病棟におけるプレアボイド症例−  [通常講演]
    沖 洋充, 清川真美, 深井敏隆, 小林道也, 荻野 修, 菅原 満, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • 高アンモニア血症に対する院内製剤供給後の治療成績評価  [通常講演]
    山下恭範, 岩井美和子, 志賀弘康, 岸野吏志, 菅原 満, 宮崎勝巳, 窪田 満, 小林邦彦
    日本薬学会第121年会(札幌) 2001年
  • 薬剤師主導による心不全患者に対するカルベジロール投与プロトコールの構築  [通常講演]
    清川真美, 岸野吏志, 深井敏隆, 高木眞弓, 米澤一也, 小林道也, 菅原 満, 宮崎勝巳, 北畠 顯
    日本薬学会第121年会(札幌) 2001年
  • α1-酸性糖蛋白質とその不均一性体に対する光学異性体薬物の立体選択的結合性  [通常講演]
    中川 勉, 伊藤 慎, 岸野吏志, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • 北大病院における治験コーディネーター業務への取り組み  [通常講演]
    橋本あきら, 高田陽美, 川合真次, 荻野 修, 菅原 満, 浅野弘恵, 木下克恵, 竹内ひとみ, 奥原芳子, 宮崎勝巳, 小柳知彦
    日本薬学会第121年会(札幌) 2001年
  • C6 glioma細胞におけるsystem A アミノ酸トランスポーターの機能特性  [通常講演]
    田中一成, 杉浦香織, 藤川世梨, 岡田直貴, 藤田卓也, 山本 昌, 菅原 満, Frederick H. Leibach, Vadivel Ganapathy
    日本薬学会第121年会(札幌) 2001年
  • 消化管内pH変動を考慮した薬物吸収評価系の改良と消化管内薬物相互作用の評価  [通常講演]
    小林道也, 佐田憲昭, 立浪綾子, 坪井 瞳, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • アミノ酸輸送担体システムAのクローニングおよび機能解析  [通常講演]
    菅原 満, Frederick H. Leibach, Vadivel Ganapathy, 宮崎勝巳
    日本薬学会第121年会(札幌) 2001年
  • Primary structure, genomic organization, and functional and electrogenic characteristics of human system N (SN1), a sodium- and proton-coupled glutamine transporter  [通常講演]
    Sugawara M, Fei Y.-J, Nakanishi T, Prasad P. D, Wang H, Leibach F. H, Ganapathy V
    ASBMB and ASPET Joint Meeting(Boston MA) 2000年
  • Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical of system A  [通常講演]
    Sugawara M, Nakanishi T, Fei Y.-J, Huang W, Ganapathy M. E, Leibach F. H, Ganapathy V
    ASBMB and ASPET Joint Meeting(Boston MA) 2000年
  • cDNA structure, genomic organization, and promoter snalysis of the mouse intestinal peptide transporter PEPT1  [通常講演]
    Ganapathy V, Fei Y.-J, Sugawara M, Ganapathy M. E, Leibach F. H
    ASBMB and ASPET Joint Meeting(Boston MA) 2000年
  • 各種イオン型薬物の小腸基底膜透過におよぼす膜電位の影響  [通常講演]
    小林道也, 吉田英人, 菅原 満, 井関 健, 宮崎勝巳
    第15回日本薬物動態学会年会(福岡) 2000年
  • 消化管内pH変動を考慮した吸収評価系によるヒト薬物動態予測  [通常講演]
    佐田憲昭, 菅原 満, 小林道也, 中 正道, 井関 健, 宮崎勝巳
    第15回日本薬物動態学会年会(福岡) 2000年
  • 薬物の生体内動態における構造相関(第49報)−消化管内pHの変動を考慮した難溶性薬物の消化管吸収評価法−  [通常講演]
    佐田憲昭, 菅原 満, 小林道也, 中 正道, 井関 健, 宮崎勝巳
    日本薬学会第120年会(岐阜) 2000年
  • Transport of gancyclovir valeate by peptide transporters PepT1 and PepT2  [通常講演]
    Ganapathy M. E, Huang W, Sugawara M, Ganapathy V, Leibach F. H
    1999 AAPS Annual Meeting(New Orleans) 1999年
  • Interaction of β-lactam antibiotics with OCTN2, an organic cation/carnitine transporter  [通常講演]
    Ganapathy M. E, Rajan D. P, Sugawara M, Iseki K, Kekuda R, Leibach F. H, Ganapathy V
    1999 AAPS Annual Meeting(New Orleans) 1999年
  • 消化管内pHの変動を考慮した薬物の消化管吸収評価法の確立  [通常講演]
    佐田憲昭, 菅原 満, 小林道也, 中 正道, 井関 健, 宮崎勝巳
    第14回日本薬物動態学会年会(浜松) 1999年
  • 高速液体クロマトグラフィーによる血清中ピルニカイジド定量法の確立  [通常講演]
    井藤達也, 新庄 一, 尾形仁子, 中川英久, 浜辺 晃, 菅原 満, 井関 健, 宮崎勝巳
    第47回日本心臓病学会学術集会(横浜) 1999年
  • 塩酸イリノテカン(CPT-11)、SN-38およびSN-38グルクロナイド定量法の確立−高速液体クロマトグラフィーによるラクトン開環体および総濃度の分離定量−  [通常講演]
    井藤達也, 関谷千尋, 高岡和夫, 藤崎博子, 菅原 満, 井関 健, 宮崎勝巳
    第16回日本TDM学会(横浜) 1999年
  • ヒト小腸およびCaco-2細胞を用いた薬物吸収性評価〜P-Glycoproteinによる排出系の異同性〜  [通常講演]
    早川智久, 菅原 満, 井関 健, 宮崎勝巳
    第14回日本薬物動態学会年会(浜松) 1999年
  • 胃癌患者における胃切除術後の薬物吸収動態  [通常講演]
    井藤達也, 福田由布子, 福島紘司, 真鍋邦彦, 秦 温信, 佐野文男, 斎藤正信, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第119年会(徳島) 1999年
  • 薬物の生体内動態における構造相関(第48報)−多剤排出蛋白を介したPSPの腎排泄−  [通常講演]
    小林道也, 藤本道夫, 西村幸穂, 井上 悟, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第119年会(徳島) 1999年
  • イオン型薬物の消化管吸収におよぼす膜表面電位の影響  [通常講演]
    黒澤 恵, 菅原 満, 井関 健, 宮崎勝巳
    第13回日本薬物動態学会年会(仙台) 1998年
  • ラット小腸H+依存性輸送タンパクの精製とその機能評価  [通常講演]
    神谷あや子, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第13回日本薬物動態学会年会(仙台) 1998年
  • 薬学部4年次学生に対する1ヶ月間病院実習の実施とその評価  [通常講演]
    小林道也, 深井敏隆, 岸野吏志, 川合真次, 菅原 満, 宮本剛典, 荻野 修, 井関 健, 宮崎勝巳
    第8回日本病院薬学会年会(横浜) 1998年
  • 高速液体クロマトグラフィーによる血中ピルジカイニド定量法の確立と有効濃度の検討  [通常講演]
    井藤達也, 福島紘司, 尾形仁子, 中川英久, 浜辺 晃, 菅原 満, 井関 健, 宮崎勝巳
    第15回日本TDM学会・学術大会(神戸) 1998年
  • 高アンモニア血症治療薬フェニル酢酸製剤の生体内動態  [通常講演]
    馬渕朋美, 板垣文雄, 橋本あきら, 岸野吏志, 菅原 満, 井関 健, 宮崎勝巳, 郡 修徳, 長坂博範, 窪田 満, 小林邦彦
    日本薬学会第118年会(京都) 1998年
  • 薬物の生体内動態における構造相関(第45報)薬物の消化管吸収に及ぼす膜表面電位の影響  [通常講演]
    黒澤 恵, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第118年会(京都) 1998年
  • 薬物の生体内動態における構造相関(第44報)難水溶性薬物の消化管吸収予測  [通常講演]
    菅原 満, 古居奈歩, 小林道也, 井関 健, 宮崎勝巳
    日本薬学会第118年会(京都) 1998年
  • 薬物の生体内動態における構造相関(第43報)LECラットにおけるフェノールスルホンフタレインの腎排泄挙動  [通常講演]
    藤本道夫, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第118年会(京都) 1998年
  • 薬物の生体内動態における構造相関(第42報)トリエンチンの尿中排泄におけるスペルミン輸送担体の寄与  [通常講演]
    藤崎博子, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第118年会(京都) 1998年
  • 経腸栄養剤投与時における薬物吸収の変動  [通常講演]
    井関 健, 浅子 恵, 金内美妃, 菅原 満, 宮崎勝巳
    日本薬剤学会第13年会(山梨) 1998年
  • 腎移植患者におけるタクロリムス血中濃度モニタリング−アセナリン併用による吸収挙動の改善−  [通常講演]
    駒井智美, 岸野吏志, 菅原 満, 井関 健, 宮崎勝巳, 竹内一郎, 野々村克也, 小柳知彦
    第11回北海道TDM研究会研究発表会(札幌) 1997年
  • ペプチド輸送担体の再構築と構造解析  [通常講演]
    米村一洋, 神谷あや子, 菅原 満, 井関 健, 宮崎勝巳
    第12回日本薬物動態学会年会(名古屋) 1997年
  • ポリアミン型薬物の腎排泄機構  [通常講演]
    小林道也, 藤崎博子, 菅原 満, 井関 健, 宮崎勝巳
    第12回日本薬物動態学会年会(名古屋) 1997年
  • Na+依存性担体輸送におよぼすカチオン型薬物の影響とその評価  [通常講演]
    加藤雅也, 菅原 満, 小林道也, 井関 健, 宮崎勝巳
    第12回日本薬物動態学会年会(名古屋) 1997年
  • 薬物の消化管吸収予測式の構築〜薬物−生体膜間の静電的相互作用をパラメーターとしたシミュレーション〜  [通常講演]
    菅原 満, 武隈 洋, 小林道也, 井関 健, 宮崎勝巳
    第19回生体膜と薬物の相互作用シンポジウム(札幌) 1997年
  • 血液透析患者におけるランソプラゾールの薬物動態  [通常講演]
    井藤達也, 稲垣真実子, 福島紘司, 岡本延彦, 安田卓二, 布施川尚, 菅原 満, 井関 健, 宮崎勝巳
    第14回日本TDM学会学術大会(浜松) 1997年
  • 第5回若手研究者の奨励招待講演;薬物−生体膜間の静電的相互作用を考慮した消化管吸収性予測式の構築  [通常講演]
    菅原 満
    日本薬学会北海道支部第108回例会(札幌) 1997年
  • 薬物の生体内動態における構造相関(第40報)−物理化学的測定値を用いた薬物の消化管吸収予測式の構築−  [通常講演]
    菅原 満, 武隈 洋, 山田晴美, 小林道也, 井関 健, 宮崎勝巳
    日本薬学会第117年会(東京) 1997年
  • 薬物の生体内動態における構造相関(第39報)−ラット腎刷子縁膜に存在するポリアミン輸送担体の特徴−  [通常講演]
    藤崎博子, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第117年会(東京) 1997年
  • 薬物の生体内動態における構造相関(第38報)−担体輸送系に及ぼすカチオン型薬物の影響−  [通常講演]
    加藤雅也, 菅原 満, 小林道也, 井関 健, 宮崎勝巳
    日本薬学会第117年会(東京) 1997年
  • 薬物の生体内動態における構造相関(第37報)−小腸刷子縁膜担体輸送系の一次再構築−  [通常講演]
    米村一洋, 山本利花, 神谷あや子, 菊地崇行, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第117年会(東京) 1997年
  • ポリアミン型薬物の腎上皮細胞膜透過機構  [通常講演]
    小林道也, 藤崎博子, 田辺 亮, 菅原 満, 井関 健, 宮崎勝巳
    第18回生体膜と薬物の相互作用シンポジウム(徳島) 1996年
  • 小腸および腎上皮細胞膜担体輸送系の再構成  [通常講演]
    菊地崇行, Naasani Imad, 菅原 満, 井関 健, 宮崎勝巳
    第18回生体膜と薬物の相互作用シンポジウム(徳島) 1996年
  • 薬物の物理化学的測定値による新規消化管吸収予測法の検討  [通常講演]
    武隈 洋, 菅原 満, 山田晴美, 小林道也, 井関 健, 宮崎勝巳
    第11回日本薬物動態学会年会(金沢) 1996年
  • 薬物の生体内動態における構造相関(第36報)−グルタミン酸の小腸刷子縁膜透過に及ぼすカチオン型薬物の影響−  [通常講演]
    菅原 満, 加藤雅也, 小林道也, 井関 健, 宮崎勝巳
    日本薬学会第116年会(金沢) 1996年
  • 薬物の生体内動態における構造相関(第35報)−ラット腎セフチブテン輸送担体の再構成−  [通常講演]
    菊池崇行, Naasani Imad, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第116年会(金沢) 1996年
  • 薬物の生体内動態における構造相関(第34報)−ポリアミン類のラット腎刷子縁膜透過機構−  [通常講演]
    小林道也, 田辺 亮, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第116年会(金沢) 1996年
  • アニオン型薬物の消化管吸収性予測式の構築−物理化学的測定値によるsimulation−  [通常講演]
    菅原 満, 武隈 洋, 小林道也, 井関 健, 宮崎勝巳
    第10回日本薬物動態学会年会(大宮) 1995年
  • 薬物の生体内動態における構造相関(第31報)刷子縁膜が認識しうるセフチブテンの構造部位  [通常講演]
    菅原 満井関, Naasani Imad, 佐藤香織, 小林道也, 菅原 満, 宮崎勝巳
    日本薬学会第115年会(仙台) 1995年
  • 薬物の生体内動態における構造相関(第30報)スパルフロキサシンの小腸刷子縁膜透過に及ぼす膜表面電位の効果  [通常講演]
    辻 華里, 平野 剛, 宮崎正三, 高田昌彦, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第115年会(仙台) 1995年
  • 薬物の生体内動態における構造相関(第29報)ジアミン型薬物のラット小腸刷子縁膜透過における構造相関  [通常講演]
    小林道也, 駿河幸恵, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第115年会(仙台) 1995年
  • Transport mechanisms of an orally active cephem, ceftibuten, in the brush-border membrane: Comparison between small intestine and kidney  [通常講演]
    Naasani I, Sugawara M, Kobayashi M, Iseki K, Miyazaki K
    The Seventh Japanese-American Conference on Pharmacokinetics and Biopharmaceutics(Hiroshima) 1994年
  • ポリアミン類のラット小腸側底膜透過機構  [通常講演]
    小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第9会日本薬物動態学会年会(広島) 1994年
  • キノロン系抗菌剤の消化管吸収および腎排泄機構  [通常講演]
    平野 剛, 宮崎正三, 高田昌彦, 菅原 満, 井関 健, 宮崎勝巳
    第9会日本薬物動態学会年会(広島) 1994年
  • イオン性薬物の小腸刷子縁膜透過におよぼす膜表面電位の影響  [通常講演]
    菅原 満, 小林道也, 井関 健, 宮崎勝巳
    第9会日本薬物動態学会年会(広島) 1994年
  • 薬物の生体内動態における構造相関(第23報)カチオン型薬物の小腸刷子縁膜透過に対する膜電位の影響  [通常講演]
    菅原 満, 及川尚子, 小林道也, 井関 健, 宮崎勝巳
    日本薬学会第114年会(東京) 1994年
  • 薬物の生体内動態における構造相関(第22報)-purine系薬物の小腸膜透過機構-  [通常講演]
    井関 健, 藤原俊恵, 小林道也, 菅原 満, 宮崎勝巳
    日本薬学会第114年会(東京) 1994年
  • 薬物の生体内動態における構造相関(第21報)経口セフェム、Ceftibutenの刷子縁膜透過機構;腎と小腸の比較  [通常講演]
    Nassani Imad, 坂本容子, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第114年会(東京) 1994年
  • アニオン型薬物の膜透過に対する膜表面電位の影響  [通常講演]
    橋本あきら, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第8回日本薬物動態学会年会(千葉) 1993年
  • 6-Mercaptopurine系薬物の小腸膜透過機構  [通常講演]
    藤原俊恵, 小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第8回日本薬物動態学会年会(千葉) 1993年
  • ポリアミン類の小腸上皮細胞膜透過機構  [通常講演]
    小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第8回日本薬物動態学会年会(千葉) 1993年
  • Wilson病治療薬trientineの病態モデルラットおよび患者における体内動態と薬理効果  [通常講演]
    井関 健, 小林道也, 菅原 満, 宮崎勝巳, 荒島真一郎, 高橋撤男, 日向平明, 岡安多香子, 松本脩三
    第96回日本小児科学会学術集会(横浜) 1993年
  • 薬物の生体内動態における構造相関(第18報)経口セフェム剤の小腸吸収に及ぼすペプチド製剤Enterued併用の影響  [通常講演]
    井関 健, 菅原 満, 佐藤佳子, 宮崎勝巳
    日本薬学会第113年会(大阪) 1993年
  • 薬物の生体内動体における構造相関(第13報)—イオン性薬物の膜透過における膜表面電荷の寄与:Caco-2による検討—  [通常講演]
    海藤功一, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第113年会(大阪) 1993年
  • カチオン型、アニオン型および両性イオン型薬物の小腸刷子縁膜透過機構における膜電位の寄与  [通常講演]
    井関 健, 菅原 満, 宮崎勝巳
    第23回薬物代謝と薬効・毒性シンポジウム(東京) 1992年
  • 薬物の生体内動体における構造相関(第9報)—ペニシリン系抗生物質の小腸刷子縁膜透過機構—  [通常講演]
    高橋雅樹, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第112年会(福岡) 1992年
  • 薬物の生体内動体における構造相関(第6報)—β-ラクタム系抗生物質の小腸刷子縁膜透過機構—  [通常講演]
    菅原 満, 佐々木誠, 戸田貴大, 井関 健, 宮崎勝巳
    日本薬学会第112年会(福岡) 1992年
  • 薬物の生体内動体における構造相関(第5報)—セフチブテンの小腸刷子縁膜透過性—  [通常講演]
    戸田貴大, 菅原 満, 井関 健, 宮崎勝巳
    日本薬学会第112年会(福岡) 1992年
  • ポリアミン類の生体膜透過機構-ラット小腸刷子縁膜を用いての検討-  [通常講演]
    小林道也, 菅原 満, 井関 健, 宮崎勝巳
    第13回生体膜と薬物の相互作用シンポジウム(東京) 1991年
  • イオン性薬物の膜透過機構  [通常講演]
    菅原 満
    第9回生物薬剤学研究会(東京) 1991年
  • 薬物の生体内動体における構造相関(第1報)—β-ラクタム系抗生物質の消化管吸収機構—  [通常講演]
    菅原 満, 戸田貴大, 井関 健, 宮崎勝巳
    日本薬学会第111年会(東京) 1991年
  • β-ラクタム系抗生物質の消化管吸収機構  [通常講演]
    菅原 満, 井関 健, 齊藤浩司, 宮崎勝巳, 有田隆一
    第20回薬物代謝と薬効・毒性シンポジウム(札幌) 1989年
  • β-ラクタム系抗生物質の小腸刷子縁膜透過性  [通常講演]
    菅原 満, 井関 健, 齊藤浩司, 宮崎勝巳, 有田隆一
    日本薬学会第110年会(名古屋) 1989年
  • β-ラクタム系抗生物質の刷子縁膜透過性と膜流動性変化の影響  [通常講演]
    井関 健, 菅原 満, 齊藤浩司, 宮崎勝巳, 有田隆一
    日本薬学会第109年会(広島) 1988年

その他活動・業績

  • 機械学習を活用した定常状態のAUC400-600mg・h/Lを目標とするバンコマイシン投与量推定モデルの構築
    宮井 貴之, 今井 俊吾, 吉村 理恵, 柏木 仁, 佐藤 夕紀, 上野 英文, 武隈 洋, 菅原 満 TDM研究 39 (2) 128 -128 2022年05月
  • 乳児へのボリコナゾール投与中に、代謝機能の発達によると考えられる著しい血中濃度低下が認められた1例
    山口 敦史, 田澤 佑基, 武隈 洋, 植木 将弘, 山田 雅文, 真鍋 淳, 菅原 満 TDM研究 39 (2) 136 -136 2022年05月
  • がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査
    熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 川本 泰之, 武隈 洋, 菅原 満, 小松 嘉人 Palliative Care Research 16 (Suppl._Hokkaido) S492 -S492 2021年10月
  • 北海道版・令和元年度次世代薬剤師指導者研修会における研修6ヵ月後のアンケート調査による行動変容からの研修効果評価
    片山 真二, 伊藤 優, 岩尾 一生, 前田 直大, 宇野 雅樹, 野田 敏宏, 山田 武志, 五十君 篤哉, 菅原 満, 竹内 伸仁, 令和元年度次世代薬剤師指導者研修会WG 日本薬剤師会学術大会講演要旨集 54回 214 -214 2021年09月
  • 大規模レセプトデータベースを用いた日本におけるTriple Whammy処方の実態解明
    今井 俊吾, 百 賢二, 柏木 仁, 宮井 貴之, 菅原 満, 武隈 洋 日本医薬品情報学会総会・学術大会講演要旨集 23回 78 -78 2021年06月
  • 熊井 正貴, 今井 俊吾, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 山田 武宏, 武隈 洋, 菅原 満 日本臨床腫瘍薬学会雑誌 20 3 -3 2021年05月
  • 医療の質向上、臨床の薬剤師による研究推進を目指した医療ビッグデータの活用 JMDCレセプトデータベースを用いた臨床研究
    武隈 洋, 今井 俊吾, 菅原 満 日本薬学会年会要旨集 141年会 S13 -3 2021年03月
  • 若手薬学研究者で加速させる感染症トランスレーショナルリサーチ バンコマイシンによる腎機能障害リスクを投与開始前に推定するためのフローチャートの構築 感染症診療におけるデータマイニング手法の活用
    宮井 貴之, 今井 俊吾, 菅原 満 日本薬学会年会要旨集 141年会 GS01 -6 2021年03月
  • 卵黄レシチンを用いた乳剤化に適した化合物の物理化学的特性
    鳥山 竜也, 佐藤 夕紀, 柏木 仁, 今井 俊吾, 武隈 洋, 菅原 満 日本薬学会年会要旨集 141年会 28V11 -pm06S 2021年03月
  • 吸収トランスポーターの機能解析へのエンテロイドの応用
    島田 美紀子, 佐藤 夕紀, 柏木 仁, 今井 俊吾, 武隈 洋, 菅原 満 日本薬学会年会要旨集 141年会 29V07 -am05S 2021年03月
  • 医療の質向上、臨床の薬剤師による研究推進を目指した医療ビッグデータの活用 JMDCレセプトデータベースを用いた臨床研究
    武隈 洋, 今井 俊吾, 菅原 満 日本薬学会年会要旨集 141年会 S13 -3 2021年03月
  • 若手薬学研究者で加速させる感染症トランスレーショナルリサーチ バンコマイシンによる腎機能障害リスクを投与開始前に推定するためのフローチャートの構築 感染症診療におけるデータマイニング手法の活用
    宮井 貴之, 今井 俊吾, 菅原 満 日本薬学会年会要旨集 141年会 GS01 -6 2021年03月
  • 卵黄レシチンを用いた乳剤化に適した化合物の物理化学的特性
    鳥山 竜也, 佐藤 夕紀, 柏木 仁, 今井 俊吾, 武隈 洋, 菅原 満 日本薬学会年会要旨集 141年会 28V11 -pm06S 2021年03月
  • 吸収トランスポーターの機能解析へのエンテロイドの応用
    島田 美紀子, 佐藤 夕紀, 柏木 仁, 今井 俊吾, 武隈 洋, 菅原 満 日本薬学会年会要旨集 141年会 29V07 -am05S 2021年03月
  • 日本におけるコルヒチンと強力なCYP3A4阻害薬/P糖蛋白質阻害薬の併用実態の解明
    今井 俊吾, 百 賢二, 柏木 仁, 宮井 貴之, 菅原 満, 武隈 洋 日本腎臓病薬物療法学会誌 9 (特別号) S140 -S140 2020年11月
  • ASTによるカルバペネム系抗菌薬および抗MRSA薬のdaily reviewが抗菌薬使用量および患者アウトカムに与える影響
    鏡 圭介, 石黒 信久, 山田 武宏, 新沼 悠介, 武隈 洋, 菅原 満, 小山田 玲子, 渡邊 翼, 早坂 かすみ, 福元 達也, 岩崎 澄央, 瀧 圭介 日本化学療法学会雑誌 68 (Suppl.A) 333 -333 2020年09月
  • 院内製造18F-FDGのエンドトキシン試験における反応干渉因子に関する検討
    小林 准, 西嶋 剣一, 大曲 茂生, 山崎 純一, 菊池 康子, 久下 裕司, 武隈 洋, 菅原 満 日本薬学会年会要旨集 140年会 26I -pm21 2020年03月
  • BCR-ABLチロシンキナーゼ阻害剤(TKI)の一時的曝露による持続的細胞増殖抑制効果の検討
    青山 剛, 武隈 洋, 今井 俊吾, 柏木 仁, 菅原 満 日本薬学会年会要旨集 140年会 27Y -am01 2020年03月 [査読無し][通常論文]
  • 高齢者における肝薬物代謝能低下時の体組成変化
    蕪木 素代子, 吉村 恵理, 宮本 康史, 今井 俊吾, 柏木 仁, 上野 英文, 菅原 満, 武隈 洋 日本薬学会年会要旨集 140年会 27Z -am11S 2020年03月 [査読無し][通常論文]
  • シクロプロパン鎖導入環状ペプチド化合物の膜透過性および吸収性の評価
    加藤 七海, 植村 真衣, 松井 耕平, 渡邉 瑞貴, 武隈 洋, 周東 智, 菅原 満 日本薬学会年会要旨集 140年会 27Z -pm13 2020年03月 [査読無し][通常論文]
  • 下顎埋伏智歯抜歯術におけるセフカペンピボキシルとアモキシシリンの手術部位感染予防効果の比較
    山神 彰, 小林 正紀, 山田 武宏, 北川 善政, 大廣 洋一, 佐藤 淳, 石黒 信久, 今井 俊吾, 武隈 洋, 菅原 満, 井関 健 日本薬学会年会要旨集 140年会 28Z -am10S 2020年03月 [査読無し][通常論文]
  • 院内製造18F-FDGのエンドトキシン試験における反応干渉因子に関する検討
    小林 准, 西嶋 剣一, 大曲 茂生, 山崎 純一, 菊池 康子, 久下 裕司, 武隈 洋, 菅原 満 日本薬学会年会要旨集 140年会 26I -pm21 2020年03月 [査読無し][通常論文]
  • BCR-ABLチロシンキナーゼ阻害剤(TKI)の一時的曝露による持続的細胞増殖抑制効果の検討
    青山 剛, 武隈 洋, 今井 俊吾, 柏木 仁, 菅原 満 日本薬学会年会要旨集 140年会 27Y -am01 2020年03月 [査読無し][通常論文]
  • 高齢者における肝薬物代謝能低下時の体組成変化
    蕪木 素代子, 吉村 恵理, 宮本 康史, 今井 俊吾, 柏木 仁, 上野 英文, 菅原 満, 武隈 洋 日本薬学会年会要旨集 140年会 27Z -am11S 2020年03月 [査読無し][通常論文]
  • シクロプロパン鎖導入環状ペプチド化合物の膜透過性および吸収性の評価
    加藤 七海, 植村 真衣, 松井 耕平, 渡邉 瑞貴, 武隈 洋, 周東 智, 菅原 満 日本薬学会年会要旨集 140年会 27Z -pm13 2020年03月 [査読無し][通常論文]
  • 下顎埋伏智歯抜歯術におけるセフカペンピボキシルとアモキシシリンの手術部位感染予防効果の比較
    山神 彰, 小林 正紀, 山田 武宏, 北川 善政, 大廣 洋一, 佐藤 淳, 石黒 信久, 今井 俊吾, 武隈 洋, 菅原 満, 井関 健 日本薬学会年会要旨集 140年会 28Z -am10S 2020年03月 [査読無し][通常論文]
  • 梨本俊亮, 八木沙織, 武田直樹, 野中美玖, 武隈洋, 菅原満, 菅原満, 佐藤夕紀 トランスポーター研究会年会抄録集 15th 2020年
  • 医療事故の再発防止への提言(第3号)に対する取り組み アドレナリン注射液0.3mg製剤の院内配置
    沖 洋充, 山崎 浩二郎, 熊井 正貴, 古藤 幸子, 本田 秀子, 根岸 淳, 菅原 満, 南須原 康行 医療の質・安全学会誌 14 (Suppl.) 498 -498 2019年11月 [査読無し][通常論文]
  • 外来化学療法における検査オーダ項目の事前確認及び提案の有益性
    大聖貴之, 西村紗綾, 山﨑浩二郎, 志賀弘康, 齋藤佳敬, 内山数貴, 坂本達彦, 武隈洋, 菅原満 第24回 札幌病院薬剤師会会員発表会講演要旨集 2019年11月 [査読無し][通常論文]
  • 牛車腎気丸によるドセタキセル誘発性末梢神経障害の予防効果
    菅野 亮太, 齋藤 佳敬, 山下 啓子, 武隈 洋, 菅原 満 第24回 札幌病院薬剤師会会員発表会講演要旨集 2019年11月 [査読無し][通常論文]
  • monthlyTC施行時のアプレピタントによる消化器症状予防・軽減効果の評価
    渡辺祐子, 齋藤佳敬, 武隈洋, 菅原満 第24回 札幌病院薬剤師会会員発表会講演要旨集 2019年11月 [査読無し][通常論文]
  • Performance Status 不良群におけるナルデメジンの有効性の検証.
    加藤信太郎, 小野田紘子, 今井俊吾, 熊井正貴, 武隈洋, 菅原満 日本緩和医療学会 第2回関西支部学術大会 2019年10月 [査読無し][通常論文]
  • 田中 寛之, 森岡 悠紀, 武隈 洋, 藤田 崇宏, 遠藤 雅之, 菅原 満 TDM研究 36 (2) 179 -179 2019年05月 [査読無し][通常論文]
  • 臨床製剤と薬学教育をめぐる現状と課題 薬剤学から臨床製剤を考える
    菅原 満 日本薬学会年会要旨集 139年会 (1) 258 -258 2019年03月 [査読無し][通常論文]
  • 定村 樹, 佐藤 夕紀, 武隈 洋, 菅原 満 日本薬学会年会要旨集 139年会 (4) 61 -61 2019年03月 [査読無し][通常論文]
  • 小関 千尋, 石川 岳彦, 佐藤 夕紀, 武隈 洋, 菅原 満 日本薬学会年会要旨集 139年会 (4) 68 -68 2019年03月 [査読無し][通常論文]
  • 八木 沙織, 梨本 俊亮, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 139年会 (4) 68 -68 2019年03月 [査読無し][通常論文]
  • 薬学実務実習前後における薬学生のコミュニケーション分析 RIAS(Roter method of interaction process analysis)を用いて
    武隈 洋, 森 綾子, 小林 正紀, 山田 勇磨, 佐藤 夕紀, 鳴海 克哉, 古堅 彩子, 菅原 満 日本薬学会年会要旨集 139年会 (4) 212 -212 2019年03月 [査読無し][通常論文]
  • エンテロイドは薬物排出トランスポーターの機能解析ツールになり得るか
    小関千尋, 石川岳彦, 佐藤夕紀, 武隈 洋, 菅原 満 第32回北海道薬物作用談話会 2018年07月 [査読無し][通常論文]
  • 佐々木真彩, 青山剛, 佐藤夕紀, 武隈洋, 菅原満 医療薬学フォーラム講演要旨集 26th 249 2018年06月 [査読無し][通常論文]
  • テアニンの製剤に含有される成分によるテアニンの消化管吸収増大機構の解明
    佐藤 夕紀, 山口 和奎, 小川 美香子, 武隈 洋, 足立 知基, 櫻田 剛史, 中川 公太, 本城 政稔, 菅原 満 日本薬剤学会年会講演要旨集 33年会 184 -184 2018年05月 [査読無し][通常論文]
  • オキサ酸を用いた乳剤化によるクルクミンの吸収改善と消化管への影響の評価
    西村悠汰, 八巻義朗, 佐藤夕紀, 武隈 洋, 丸山真吾, 菅原 満 日本薬学会北海道支部第145 回例会 2018年05月 [査読無し][通常論文]
  • 肝遊離細胞サンドイッチ培養法を用いたカルベジロールの輸送および代謝における光学異性体間相互作用の解析
    伊藤 圭祐, 佐々木 萌子, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 138年会 (4) 51 -51 2018年03月 [査読無し][通常論文]
  • オキサ酸を乳化剤として用いたCoenzyme Q10乳剤の性質とその消化管吸収性
    八巻 義朗, 西村 悠汰, 横山 さや香, 佐藤 夕紀, 武隈 洋, 丸山 真吾, 菅原 満 日本薬学会年会要旨集 138年会 (4) 86 -86 2018年03月 [査読無し][通常論文]
  • 後期高齢者における腎機能推定式の乖離とその補正法の確立
    蕪木 素代子, 吉村 恵理, 小嶋 希望, 上野 英文, 菅原 満, 武隈 洋 日本薬学会年会要旨集 138年会 (4) 174 -174 2018年03月 [査読無し][通常論文]
  • 植村 真衣, 加藤 七海, 松井 耕平, 桑原 智希, 渡邉 瑞貴, 福田 隼, 武隈 洋, 菅原 満, 周東 智 日本薬学会年会要旨集 138年会 (2) 116 -116 2018年03月 [査読無し][通常論文]
  • 伊藤圭祐, 佐々木萌子, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 日本薬学会年会要旨集(CD-ROM) 138th (4) ROMBUNNO.27C‐am03 -51 2018年03月 [査読無し][通常論文]
  • 佐藤夕紀, 中村公則, 小関千尋, 石川岳彦, 島田美紀子, 横井友樹, 本間直幸, 森山隆則, 菅原満 トランスポーター研究会年会抄録集 13th 2018年
  • 佐藤夕紀, 梨本俊亮, 武隈洋, 平野卓哉, 野田敏宏, 須田範行, 井関健, 盛本修司, 菅原満 日本医療薬学会年会講演要旨集(Web) 28 2018年
  • 高齢者における腎機能推定式の補正法の確立
    蕪木素代子, 武隈 洋, 吉村恵理, 小嶋希望, 上野博文, 菅原 満 第31回北海道TDM研究会研究発表会 2017年11月 [査読無し][通常論文]
  • ヒトK562細胞に対するBCR-ABLチロシンキナーゼインヒビター(TKIs)Washout後持続的細胞増殖抑制効果の検証
    青山 剛, 武隈 洋, 佐藤夕紀, 鷲見正人, 菅原 満 第31回北海道TDM研究会研究発表会 2017年11月 [査読無し][通常論文]
  • 脳梗塞を合併したレビー小体型認知症に対してリバスチグミンからの切り替えで低用量長期間投与ガランタミンが有効だった1症例
    濱野 宏美, 土井 正剛, 武隈 洋, 菅原 満, 一木 崇宏 日本薬剤師会学術大会講演要旨集 50回 [P -418] 2017年10月
  • 菅原 満 薬局 68 (9) 3026 -3031 2017年08月 [査読無し][通常論文]
     
    <Key Points>胃や小腸の切除やそれに伴う再建術により、薬物の消化管吸収に変動を及ぼす生理機能が影響を受ける。吸収やバイオアベイラビリティの増大や減少が認められている薬物があることから、それらの薬物では、治療効果の変動や副作用発現などを注意深くモニターする必要がある。(著者抄録)
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    山口 和奎, 佐藤 夕紀, 武隈 洋, 櫻田 剛史, 中川 公太, 本城 政稔, 菅原 満 日本薬学会年会要旨集 137年会 (4) 67 -67 2017年03月 [査読無し][通常論文]
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  • 佐々木 萌子, 武隈 洋, 佐藤 夕紀, 鷲見 正人, 菅原 満 日本薬学会年会要旨集 137年会 (4) 63 -63 2017年03月 [査読無し][通常論文]
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    中村雄亮, 齊藤嘉津彦, 青山剛, 武隈 洋, 菅原 満 第30回北海道TDM研究会研究発表会 2016年11月26日 [査読無し][通常論文]
  • piperacillin/tazobactamとcefepimeの急性腎障害発症に関する後ろ向き観察 比較研究
    門村将太, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満, 福田由布子, 井藤達也 第30回北海道TDM研究会研究発表会 2016年11月26日 [査読無し][通常論文]
  • 青沼 和隆, 志賀 剛, 新 博次, 池田 隆徳, 市田 蕗子, 上野 和行, 越前 宏俊, 栄田 敏之, 清水 渉, 菅原 満, 土下 喜正, 土岐 浩介, 戸塚 恭一, 萩原 誠久, 長谷川 純一, 林 秀晴, 平尾 見三, 前田 頼伸, 松本 直樹, 渡邉 英一, 笠井 英史, 篠原 徳子, 杉山 篤, 鈴木 敦, 住友 直方, 関口 幸夫, 高橋 尚彦, 野上 昭彦, 橋口 正行, 平田 純生, 松本 宜明, 湯川 栄二, 伊藤 宏, 井上 博, 大江 透, 篠崎 公一, 田中 一彦, 本間 真人, 堀江 稔, 三浦 崇則, 日本循環器学会, 日本TDM学会 TDM研究 33 (3) 123 -157 2016年09月 [査読無し][通常論文]
  • 日本循環器学会/日本TDM学会合同ガイドライン(2013-2014年度合同研究班報告)【ダイジェスト版】 2015年版 循環器薬の薬物血中濃度モニタリングに関するガイドライン
    青沼 和隆, 志賀 剛, 新 博次, 池田 隆徳, 市田 蕗子, 上野 和行, 越前 宏俊, 栄田 敏之, 清水 渉, 菅原 満, 土下 喜正, 土岐 浩介, 戸塚 恭一, 萩原 誠久, 長谷川 純一, 林 秀晴, 平尾 見三, 前田 頼伸, 松本 直樹, 渡邉 英一, 笠井 英史, 篠原 徳子, 杉山 篤, 鈴木 敦, 住友 直方, 関口 幸夫, 高橋 尚彦, 野上 昭彦, 橋口 正行, 平田 純生, 松本 宜明, 湯川 栄二, 伊藤 宏, 井上 博, 大江 透, 篠崎 公一, 田中 一彦, 本間 真人, 堀江 稔, 三浦 崇則, 日本循環器学会, 日本TDM学会 TDM研究 33 (3) 123 -157 2016年09月 [査読無し][通常論文]
  • 田中 寛之, 平賀 博明, 武隈 洋, 三浪 圭太, 原林 透, 永森 聡, 遠藤 雅之, 菅原 満 日本整形外科学会雑誌 90 (6) S1214 -S1214 2016年06月 [査読無し][通常論文]
  • コレステロールを含有する乳剤によるコエンザイムQ10の吸収改善
    佐藤 夕紀, 八巻 義朗, 竹川 悠人, 武隈 洋, 菅原 満 日本薬剤学会年会講演要旨集 31年会 186 -186 2016年05月 [査読無し][通常論文]
  • 元茂 拓法, 田中 寛之, 森岡 悠紀, 武隈 洋, 遠藤 雅之, 菅原 満, 黒澤 光俊 TDM研究 33 (2) 194 -194 2016年05月 [査読無し][通常論文]
  • 先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発 国立大学における実践的医療薬学教育プログラム及びチーム医療・地域医療プログラムの開発
    小澤 光一郎, 中嶋 幹郎, 菅原 満, 関根 祐子 日本薬学会年会要旨集 136年会 (1) 213 -213 2016年03月
  • 脂質異常症治療薬エゼチミブによるα-トコフェロールの消化管吸収抑制とその回避策
    梨本 俊亮, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 136年会 (4) 55 -55 2016年03月 [査読無し][通常論文]
  • 小腸コレステロールトランスポーターNPC1L1 (Niemann-Pick C1-Like 1)を介したCoenzyme Q10の消化管吸収改善
    佐藤夕紀, 八巻義朗, 横山さや香, 竹川悠人, 鷲見正人, 武隈洋, 菅原満 第13回日本コエンザイムQ協会研究会 2016年02月02日 [査読無し][通常論文]
  • 日本循環器学会/日本TDM学会合同ガイドライン(2013-2014年度合同研究班報告) 2015年版 循環器薬の薬物血中濃度モニタリングに関するガイドライン
    青沼 和隆, 志賀 剛, 新 博次, 池田 隆徳, 市田 蕗子, 上野 和行, 越前 宏俊, 栄田 敏之, 清水 渉, 菅原 満, 土下 喜正, 土岐 浩介, 戸塚 恭一, 萩原 誠久, 長谷川 純一, 林 秀晴, 平尾 見三, 前田 頼伸, 松本 直樹, 渡邉 英一, 笠井 英史, 篠原 徳子, 杉山 篤, 鈴木 敦, 住友 直方, 関口 幸夫, 高橋 尚彦, 野上 昭彦, 橋口 正行, 平田 純生, 松本 宜明, 湯川 栄二, 伊藤 宏, 井上 博, 大江 透, 篠崎 公一, 田中 一彦, 本間 真人, 堀江 稔, 三浦 崇則, 日本循環器学会, 日本TDM学会 循環器病ガイドシリーズ 2015 (循環器薬の薬物血中濃度モニタリングに関するガイドライン) 3 -54 2016年02月 [査読無し][通常論文]
  • 日本循環器学会/日本TDM学会合同ガイドライン(2013-2014年度合同研究班報告)【ダイジェスト版】2015年版 循環器薬の薬物血中濃度モニタリングに関するガイドライン
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  • 武隈洋, 石坂悠, 佐藤夕紀, 鷲見正人, 菅原満 日本医療薬学会年会講演要旨集(Web) 26 2016年
  • 薬剤師会と大学の連携が保険調剤薬局での無菌調剤業務の推進に及ぼす効果
    柴山 良彦, 竹内 伸仁, 菅原 満, 井関 健 日本薬剤師会学術大会講演要旨集 48回 421 -421 2015年11月 [査読無し][通常論文]
  • 本間 直幸, 山日 千明, 面 すみれ, 佐藤 夕紀, 菅原 満, 森山 隆則 日本未病システム学会学術総会抄録集 22回 119 -119 2015年09月 [査読無し][通常論文]
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    造血幹細胞移植時の抗がん剤併用療法における投与量および薬物曝露順序の最適化について検討した。成人急性リンパ性白血病(ALL)およびその類縁疾患に対し、中等量エトポシド(VP-16)/シクロホスファミド(CY)/全身放射線照射(TBI)前処置を用いた同種造血幹細胞移植を施行した21例を対象とした。VP-16の薬物動態は個体差が大きく、最高血中濃度(Cmax)とサイトメガロウイルス(CMV)感染との関建性が示唆された。ROC曲線解析から、Cmaxのカットオフ値は80.8μg/mLと算出した。また、K-562/P-gp細胞への低濃度4-ヒドロペルオキシシクロホスファミドの事前曝露によりVP-16の感受性が高いS期の細胞が増大し、VP-16の殺細胞効果が増強することが示唆された。
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    北海道大学では、薬剤師を対象とした生涯研修プログラム「医療薬学講座〜在宅医療を中心に〜」に参加した学生へのアンケート調査を行った。その結果より、関心の高かったバイタルサインやフィジカルアセスメントに関して、長期実務実習開始前にある程度の知識と技能を習得する必要があると考え、事前実習での学習プログラムについて充実を図ることとした。それに先立ち、附属病院薬剤部が企画した研究会に薬学部教員も参加し、実習に必要な項目と方法について検討、プログラムを作成した。一方、模擬患者養成事業で行っているシナリオ練習に、実務実習終了後の学生(大学院生を含む)が薬剤師役で参加し、より複雑な症例を取り入れることで、アドバンスト医療コミュニケーションプログラムとしてのトライアルとした。(著者抄録)
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  • エゼチミブ(ゼチーア)が機能性食品成分α-トコフェロールの吸収に与える影響
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  • 乳剤化によるコエンザイムQ10の消化管吸収改善
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  • 先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発 国立大学における「実践的医療薬学教育プログラム」および「チーム医療・地域医療プログラム」の開発
    小澤 光一郎, 中嶋 幹郎, 菅原 満, 関根 祐子 日本薬学会年会要旨集 135年会 (1) 231 -231 2015年03月
  • Niemann-Pick C1 Like-1(NPC1L1)を標的とした乳剤化による難吸収性物質の吸収改善
    竹川 悠人, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 135年会 (4) 76 -76 2015年03月 [査読無し][通常論文]
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  • 菅原 満 薬局 66 (1) 34 -35 2015年01月 [査読無し][通常論文]
     
    <Key Points>妊娠時における薬物吸収の変動に関しては、妊娠による生理的諸因子の変動に関連付けて説明されている場合が多い。対象となる薬物の物理化学的な性質や吸収のメカニズムを把握しておくことが重要である。(著者抄録)
  • 本間 直幸, 山日 千明, 面 すみれ, 佐藤 夕紀, 菅原 満, 村田 清志, 山口 喜久二, 森山 隆則 機能性食品と薬理栄養 8 (5) 436 -436 2014年12月 [査読無し][通常論文]
  • UDP-グルクロン酸転移酵素の生細胞と細胞破砕液での代謝活性の比較
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  • 石坂 悠, 武隈 洋, 吉村 恵理, 吉田 憲史, 小嶋 希望, 上野 英文, 菅原 満 日本医療薬学会年会講演要旨集 24 244 -244 2014年08月25日
  • UGT1A1 p.P364L変異体および UGT2B7 p.P366L変異体の光学異性体認識性
    依田めぐみ, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第28回北海道薬物作用談話会(札幌) 2014年07月19日 [査読無し][通常論文]
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    早風郁美, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第28回北海道薬物作用談話会(札幌) 2014年07月19日 [査読無し][通常論文]
  • 田澤佑基, 武隈洋, 佐藤夕紀, 鷲見正人, 笠師久美子, 井関健, 菅原満 医療薬学フォーラム講演要旨集 22nd 242 2014年06月 [査読無し][通常論文]
  • 細胞周期変化がエトポシド(VP-16)の殺細胞効果に与える影響
    田澤佑基, 吉岡美咲, 武隈 洋, 佐藤夕紀, 鷲見 正人, 菅原 満 日本薬学会北海道支部第141回例会(札幌) 2014年05月24日 [査読無し][通常論文]
  • 田中 寛之, 木村 雄太, 川口 啓之, 武隈 洋, 高崎 雅彦, 菅原 満 TDM研究 31 (3) 169 -169 2014年05月 [査読無し][通常論文]
  • 先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発 実践的医療薬学教育プログラム及びチーム医療・地域医療プログラム
    菅原 満 日本薬学会年会要旨集 134年会 (1) 150 -150 2014年03月 [査読無し][通常論文]
  • Coenzyme Q10の消化管吸収改善
    佐藤夕紀, 能登数馬, 竹川悠人, 鷲見正人, 武隈 洋, 菅原 満 特定非営利活動法人 日本コエンザイムQ 協会 第11回研究会プログラム(東京) 2014年01月28日 [査読無し][通常論文]
  • Caco-2細胞におけるNPC1L1を介したコレステロール輸送の特徴
    阿部沙也華, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会(札幌) 2013年11月30日 [査読無し][通常論文]
  • 薬物曝露による細胞周期変化が細胞周期依存性の抗癌剤の作用に与える影響
    吉岡美咲, 田澤佑基, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会(札幌) 2013年11月30日 [査読無し][通常論文]
  • テアニンの体内動態および吸収機構の解明
    亀田佑生, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会(札幌) 2013年11月30日 [査読無し][通常論文]
  • 竹川 悠人, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本医療薬学会年会講演要旨集 23 219 -219 2013年08月28日
  • 抗アレルギー薬の使用実態調査およびそのアレルギー性咳嗽への適用に関する疫学的研究
    武隈 洋, 高地 里佳, 野田 敏宏, 平野 卓哉, 菅原 満 日本医薬品情報学会総会・学術大会講演要旨集 16回 132 -132 2013年08月 [査読無し][通常論文]
  • 難吸収性ポリフェノールの乳剤化によるバイオアベイラビリティ改善
    星山博俊, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第27回北海道薬物作用談話会(江別) 2013年07月20日 [査読無し][通常論文]
  • Niemann-pick C1 Like-1 (NPC1L1) を介した難吸収性物質の吸収改善へのアプローチ
    竹川悠人, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会北海道支部第140回例会(札幌) 2013年05月18日 [査読無し][通常論文]
  • 熱力学的手法を用いた多剤排出輸送担体の基質探索の検討
    森岡悠紀, 鷲見正人, 佐藤夕紀, 武隈洋, 菅原満 日本薬学会北海道支部第140回例会(札幌) 2013年05月18日 [査読無し][通常論文]
  • hOATPs/rOatps を介するミコフェノール酸グルクロナイドの輸送特性の種差
    坂本達彦, 鷲見正人, 佐藤夕紀, 武隈洋, 菅原満 日本薬学会北海道支部第140回例会(札幌) 2013年05月 [査読無し][通常論文]
  • 黄斑色素成分ルテインのヒト網膜上皮細胞内への取り込み機構の解明
    佐藤 夕紀, 近藤 有, 武隈 洋, 菅原 満 日本薬剤学会年会講演要旨集 28年会 272 -272 2013年04月 [査読無し][通常論文]
  • 国立大学博士課程における「チーム医療・地域医療モデル教育プログラム」の開発
    関根 祐子, 菅原 満, 小澤 光一郎, 中嶋 幹郎 日本薬学会年会要旨集 133年会 (1) 270 -270 2013年03月
  • 高田 一輝, 田澤 佑基, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 133年会 (4) 78 -78 2013年03月 [査読無し][通常論文]
  • 高地 里佳, 石坂 悠, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 133年会 (4) 153 -153 2013年03月 [査読無し][通常論文]
  • シタラビンの白血病細胞内移行に対するエトポシドの影響
    高田一輝, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第26回北海道TDM研究会研究発表会(札幌) 2012年12月 [査読無し][通常論文]
  • テアニンの脳移行に関与するトランスポーター
    川守田渉, 亀田佑生, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満 第26回北海道薬物作用談話会(札幌) 2012年07月 [査読無し][通常論文]
  • 粒子径に着目した CoQ10 の乳剤化による吸収改善
    能登数馬, 佐藤夕紀, 武隈 洋, 菅原 満 日本薬学会北海道支部第138回例会(札幌) 2012年06月 [査読無し][通常論文]
  • 先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発 国立大学における「実践的医療薬学教育プログラム」の開発
    中嶋 幹郎, 菅原 満, 関根 祐子, 小澤 光一郎 日本薬学会年会要旨集 132年会 (1) 190 -190 2012年03月
  • 臼窪 一平, 田澤 佑基, 佐藤 夕紀, 鷲見 正人, 柴山 良彦, 武隈 洋, 菅原 満 日本薬学会年会要旨集 132年会 (4) 200 -200 2012年03月 [査読無し][通常論文]
  • 田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈洋, 重松明男, 笠師久美子, 山田武宏, 田中淳司, 橋野聡, 井関健, 今村雅寛, 菅原満 日本造血細胞移植学会総会プログラム・抄録集 34th 224 2012年02月01日 [査読無し][通常論文]
  • エトポシド/シクロホスファミド併用の殺細胞効果に及ぼす曝露順序の影響 ~白血病由来 K-562 細胞及び P-糖タンパク質発現株を用いた検討~
    田澤佑基, 臼窪一平, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満 日本薬学会北海道支部第137回例会(札幌) 2011年12月 [査読無し][通常論文]
  • 抗酸化作用を有する食品成分ルテインの乳化による消化管吸収改善
    佐藤 夕紀, 武隈 洋, 井関 健, 菅原 満 機能性食品と薬理栄養 7 (1) 89 -89 2011年12月 [査読無し][通常論文]
  • 長田貴之, 柴山良彦, 熊井正貴, 山田武宏, 笠師久美子, 菅原満, 井関健 医療薬学フォーラム講演要旨集 19th 186 2011年07月 [査読無し][通常論文]
  • 菅原 満 薬局 62 (7) 2777 -2780 2011年06月 [査読無し][通常論文]
     
    <Key Points>◎乳児の薬物吸収性に関する情報は乏しく、薬物動態に関わる生理機能の新生児・乳児と成人との間の違いを把握する必要がある。◎胃内pHと消化管内の移動速度は、現在までに明らかにされている重要な要因である。◎消化管に発現するトランスポーターと代謝酵素の活性は重要な要因と考えられるが、現在のところ詳細は不明であり、具体的なエビデンスに乏しい。(著者抄録)
  • 田澤 佑基, 松村 一仙, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 重松 明男, 笠師 久美子, 山田 武宏, 井関 健, 今村 雅寛, 菅原 満 TDM研究 28 (3) s203 -s203 2011年06月 [査読無し][通常論文]
  • 菅原 満 アレルギー 60 (3-4) 402 -402 2011年04月 [査読無し][通常論文]
  • 先導的薬剤師養成に向けた実践的アドバンスト教育プログラムの共同開発 国立大学における「実践的医療薬学教育プログラム」の現状
    小澤 光一郎, 菅原 満, 関根 祐子, 中嶋 幹郎 日本薬学会年会要旨集 131年会 (1) 156 -156 2011年03月
  • ルテインの乳化による消化管吸収改善
    佐藤 夕紀, 鈴木 里彩, 武隈 洋, 井関 健, 菅原 満 日本薬学会年会要旨集 131年会 (4) 165 -165 2011年03月 [査読無し][通常論文]
  • ソラフェニブおよびスニチニブのMRP2(ABCC2)に対する基質特異性
    柴山 良彦, 中野 公, 前田 弘志, 田口 美雪, 池田 龍二, 菅原 満, 井関 健, 武田 泰夫, 山田 勝士 日本薬学会年会要旨集 131年会 (4) 288 -288 2011年03月 [査読無し][通常論文]
  • 乗り物酔い様の浮遊感を伴うオピオイドの難治性嘔気にペロスピロンが有効であった症例
    長田 貴之, 熊井 正貴, 柴山 良彦, 山田 武宏, 笠師 久美子, 菅原 満, 井関 健 日本薬学会年会要旨集 131年会 (4) 293 -293 2011年03月 [査読無し][通常論文]
  • テアニンの消化管吸収に関与するトランスポーター
    川守田 渉, 堀田 雄也, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 131年会 (4) 165 -165 2011年03月 [査読無し][通常論文]
  • 田澤 佑基, 松村 一仙, 笠師 久美子, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 井関 健, 菅原 満 日本薬学会年会要旨集 131年会 (4) 178 -178 2011年03月 [査読無し][通常論文]
  • 乳児と成人との薬物動態の違い-① 吸収過程
    菅原 満 薬局別冊 62 (7) 55 -58 2011年 [査読無し][通常論文]
  • 医療薬学ブラッシュアップ講座 薬物の体内動態に関する最近の話題-4 腎機能と薬物動態
    菅原 満 道薬誌 28 (2) 7 -11 2011年 [査読無し][通常論文]
  • 医療薬学ブラッシュアップ講座 薬物の体内動態に関する最近の話題-3 経口バイオアベイラビリティ
    菅原 満 道薬誌 28 (1) 32 -37 2011年 [査読無し][通常論文]
  • マイクロRNA126、210が抗がん薬感受性に及ぼす影響
    柴山 良彦, 田口 深雪, 池田 龍二, 古川 龍彦, 菅原 満, 井関 健, 武田 泰生, 山田 勝士 臨床薬理 41 (Suppl.) S254 -S254 2010年11月 [査読無し][通常論文]
  • 菅原 満 TDM研究 27 (3) s56 -s56 2010年06月 [査読無し][通常論文]
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    小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2628 (2628) 9 -12 2010年05月 [査読無し][通常論文]
  • Daisuke Fukumori, Moto Fukai, Kenji Wakayama, Kenichiro Yamashita, Shinya Ueki, Mitsuru Sugawara, Sanae Haga, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo AMERICAN JOURNAL OF TRANSPLANTATION 10 496 -497 2010年04月 [査読無し][通常論文]
  • Moto Fukai, Kenji Wakayama, Daisuke Fukumori, Kenichiro Yamashita, Mitsuru Sugawara, Sanae Haga, Ueki Gentaro Hirokata, Hiroyuki Furukawa, Michitaka Ozaki, Satoru Todo AMERICAN JOURNAL OF TRANSPLANTATION 10 492 -493 2010年04月 [査読無し][通常論文]
  • TDM実践シリーズ 免疫抑制剤ミコフェノール酸モフェチル
    武隈 洋, 菅原 満, 小林 道也, 唯野 貢司, 野村 憲和, 北海道TDM研究会 薬事新報 (2623) 345 -350 2010年04月 [査読無し][通常論文]
  • 堀田 雄也, 武隈 洋, 菅原 満 薬剤学: 生命とくすり 70 (Suppl.) 117 -117 2010年04月 [査読無し][通常論文]
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    菅原 満, 武隈 洋, 小林 道也, 唯野 貢司, 野村 憲和 薬事新報 2626 (2626) 31 -36 2010年04月 [査読無し][通常論文]
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    八木澤 啓司, 武隈 洋, 菅原 満 日本薬学会年会要旨集 130年会 (4) 200 -200 2010年03月 [査読無し][通常論文]
  • 高橋 夏子, 武隈 洋, 小林 正紀, 板垣 史郎, 菅原 満, 井関 健 日本薬学会年会要旨集 130年会 (4) 298 -298 2010年03月 [査読無し][通常論文]
  • 武隈 洋, 小林 正紀, 山田 勇磨, 板垣 史郎, 吉田 和幸, 井関 健, 菅原 満 日本薬学会年会要旨集 130年会 (4) 346 -346 2010年03月 [査読無し][通常論文]
  • TDM実践シリーズ(その他4) ワルファリン
    山崎 将英, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和 薬事新報 2621 (2621) 9 -15 2010年03月 [査読無し][通常論文]
  • TDM実践シリーズ その他 精神疾患治療薬
    岩尾 一生, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2619 (2619) 9 -13 2010年03月 [査読無し][通常論文]
  • TDM実践シリーズ(その他2) 塩酸イリノテカンとTDM
    田中 寛之, 小林 道也, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2617 (2617) 9 -12 2010年02月 [査読無し][通常論文]
  • TDM実践シリーズ その他 抗がん剤
    井藤 達也, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和 薬事新報 2615 (2615) 9 -14 2010年02月 [査読無し][通常論文]
  • 医療薬学ブラッシュアップ講座 薬物の体内動態に関する最近の話題-2 薬物の消化管吸収とトランスポーター
    菅原 満 道薬誌 27 (12) 4 -9 2010年 [査読無し][通常論文]
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    菅原 満 道薬誌 27 (11) 4 -9 2010年 [査読無し][通常論文]
  • TDM実践シリーズ(17)免疫抑制剤①ミコフェノール酸モフェチル
    武隈 洋, 菅原 満, 小林道也, 唯野貢司, 野村憲和 薬事新報 2623 9 -14 2010年 [査読無し][通常論文]
  • TDM実践シリーズ 抗真菌薬
    野田 久美子, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和 薬事新報 2613 (2613) 27 -31 2010年01月 [査読無し][通常論文]
  • TDM実践シリーズ 抗生物質製剤(2)
    横山 敏紀, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2611 (2611) 9 -14 2010年01月 [査読無し][通常論文]
  • TDM実践シリーズ 抗生物質製剤(1)
    國本 雄介, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2608 (2608) 9 -13 2009年12月 [査読無し][通常論文]
  • TDM実践シリーズ 抗不整脈薬(2)
    後藤 仁和, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2606 (2606) 9 -13 2009年12月 [査読無し][通常論文]
  • ボリコナゾールの血漿中濃度および髄液移行性をモニタリングした脳クリプトコックス症例
    田島宏恵, 武隈 洋, 沖 洋充, 八島萌美, 秋本幸子, 菅原 満, 井関 健 第23回北海道TDM研究会研究発表会(札幌) 2009年11月 [査読無し][通常論文]
  • 腎移植患者において腎機能の変動がミコフェノール酸体内動態に与える影響
    大谷 薫, 武隈 洋, 原田幸子, 福澤信之, 下田直彦, 三浦正義, 菅原 満, 野々村克也, 井関 健 第23回北海道TDM研究会研究発表会(札幌) 2009年11月 [査読無し][通常論文]
  • TDM実践シリーズ 抗不整脈薬(1)
    中村 寛, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2604 (2604) 9 -13 2009年11月 [査読無し][通常論文]
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    今田 愛也, 野村 憲和, 小林 道也, 唯野 貢司, 菅原 満 薬事新報 2602 (2602) 9 -13 2009年11月 [査読無し][通常論文]
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    相馬 まゆ子, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2600 (2600) 9 -14 2009年10月 [査読無し][通常論文]
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    山田 和範, 河内 邦仁, 山澤 裕司, 小林 道也, 唯野 貢司, 菅原 満, 野村 憲和, 北海道TDM研究会 薬事新報 2597 (2597) 31 -37 2009年10月 [査読無し][通常論文]
  • 齋藤 佳敬, 志賀 弘康, 小林 正紀, 須田 範行, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 19 (0) 281 -281 2009年09月15日 [査読無し][通常論文]
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    齊藤 嘉津彦, 野村 憲和, 小林 道也, 唯野 貢司, 菅原 満 薬事新報 2595 (2595) 9 -12 2009年09月 [査読無し][通常論文]
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    板垣 史郎, 菅原 満, 唯野 貢司, 小林 道也, 野村 憲和, 北海道TDM研究会 薬事新報 2593 (2593) 9 -14 2009年09月 [査読無し][通常論文]
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    戸田 貴大, 野村 憲和, 小林 道也, 唯野 貢司, 菅原 満, 北海道TDM研究会 薬事新報 (2591) 896 -901 2009年08月 [査読無し][通常論文]
  • 武隈 洋, 加藤 貴志, 漆畑 英樹, 小松 幹, 高畑 雅彦, 菅原 満, 三浪 明男, 井関 健 TDM研究 26 (3) s149 -s149 2009年06月 [査読無し][通常論文]
  • 李 暁光, 武隈 洋, 山崎 浩二郎, 西村 あや子, 菅原 満, 井関 健 TDM研究 26 (3) s170 -s170 2009年06月 [査読無し][通常論文]
  • 野田 久美子, 田中 寛之, 山澤 裕司, 齊藤 嘉津彦, 小林 道也, 菅原 満, 唯野 貢司 TDM研究 26 (3) s173 -s173 2009年06月 [査読無し][通常論文]
  • 大谷 薫, 武隈 洋, 原田 幸子, 下田 直彦, 三浦 正義, 菅原 満, 野々村 克也, 井関 健 TDM研究 26 (3) s208 -s208 2009年06月 [査読無し][通常論文]
  • 難水溶性薬物の乳剤化とその消化管吸収性に及ぼす胆汁の影響
    武藤花見, 今井智子, 中山淳司, 鈴木美香, 武隈 洋, 井関 健, 菅原 満 日本薬学会北海道支部第132回例会(札幌) 2009年05月 [査読無し][通常論文]
  • Na+/モノカルボン酸共輸送担体(SMCT1)の基質認識機構における構造活性相関
    宮内 正二, 駄馬崎 泰洋, 菅原 満, Gopal Elangovan, Ganapathy Vadivel 日本薬学会年会要旨集 129年会 (4) 260 -260 2009年03月
  • 若山 顕治, 深井 原, 山下 健一郎, 後藤 了一, 植木 伸也, 福森 大介, 柴崎 晋, 大浦 哲, 廣方 玄太郎, 芳賀 早苗, 谷口 雅彦, 鈴木 友己, 嶋村 剛, 松下 道明, 古川 博之, 尾崎 倫孝, 藤堂 省, 小野 太祐, 絹川 真太郎, 筒井 裕之, 菅原 満 日本外科学会雑誌 110 (臨増2) 709 -709 2009年02月 [査読無し][通常論文]
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  • Kenji Wakayama, Moto Fukai, Kenichiro Yamashita, Daisuke Fukumori, Susumu Shibasaki, Gentaro Hirokata, Tomohiro Shibata, Tetsu Oura, Ryoichi Goto, Masahiko Taniguchi, Tomomi Suzuki, Tsuyoshi Shimamura, Michiaki Matsushita, Hiroyuki Furukawa, Michitaka Ozaki, Taisuke Ono, Mitsuru Sugawara, Satoru Todo AMERICAN JOURNAL OF TRANSPLANTATION 9 491 -491 2009年 [査読無し][通常論文]
  • Moto Fukai, Kenichiro Yamashita, Kenji Wakayama, Daisuke Fukumori, Ryoichi Goto, Sanae Haga, Gentaro Hirokata, Shigeru Nakakimura, Mitsuru Sugawara, Hirofumi Kamachi, Tomomi Suzuki, Tsuyoshi Shimamura, Hiroyuki Furukawa, Michiaki Matsushita, Michitaka Ozaki, Satoru Todo AMERICAN JOURNAL OF TRANSPLANTATION 9 581 -581 2009年 [査読無し][通常論文]
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    笠師 久美子, 柏崎 晴彦, 阿部 貴恵, 重松 明男, 池田 陽子, 上野 あさひ, 菅原 満, 井関 健 静脈経腸栄養 24 (1) 345 -345 2009年01月 [査読無し][通常論文]
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    戸田貴大, 野村憲和, 小林道也, 唯野貢司, 菅原 満 薬事新報 2591 (25) 30 2009年 [査読無し][通常論文]
  • 処方せん発行時の抗MRSA薬初期投与設計による医師への情報提供の有用性
    木村俊也, 山崎浩二郎, 西村あや子, 横田亜季, 小笠原貴子, 大崎由美子, 執行聡美, 清川真美, 宮本剛典, 菅原 満, 井関 健 北海道病院薬剤師会誌 76 27 -30 2009年 [査読無し][通常論文]
  • カルベジロールの体内動態に及ぼす UGT遺伝子多型およびエナンチオマー間の 相互阻害作用の影響
    武隈 洋, 武中 徹, 八木澤啓司, 井幡圭佑, 菅原 満 UGT研究会(福岡) 2008年10月 [査読無し][通常論文]
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  • 渡辺 祐子, 山本 千秋, 下山 哲哉, 小林 正紀, 板垣 史郎, 菅原 満, 平野 剛, 井関 健 日本医療薬学会年会講演要旨集 18 (0) 310 -310 2008年09月01日 [査読無し][通常論文]
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  • 抗MRSA薬テイコプラニンの初期投与設計による適正使用への関わり
    木村 俊也, 山崎 浩二郎, 西村 あや子, 坪内 孝敏, 横田 亜季, 小笠原 貴子, 大崎 由美子, 執行 聡美, 清川 真美, 宮本 剛典, 武隈 洋, 菅原 満, 井関 健 TDM研究 25 (3) s213 -s213 2008年06月 [査読無し][通常論文]
  • 武藤 花見, 鈴木 美香, 武隈 洋, 井関 健, 菅原 満 薬剤学: 生命とくすり 68 (Suppl.) 249 -249 2008年04月 [査読無し][通常論文]
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    川岸 亨, 熊井 正貴, 齋藤 京之, 笠師 久美子, 菅原 満, 井関 健 日本薬学会年会要旨集 128年会 (4) 207 -207 2008年03月
  • 化膿性脊椎炎に対するリネゾリドの臨床効果と脊椎への移行性
    加藤 貴志, 菅原 満, 井関 健, 武隈 洋, 高畑 雅彦, 小松 幹, 伊東 学, 三浪 明男 日本薬学会年会要旨集 128年会 (4) 85 -85 2008年03月 [査読無し][通常論文]
  • 齋藤 佳敬, 榊原 則寛, 志賀 弘康, 沖 洋充, 小林 正紀, 川合 真次, 深井 敏隆, 菅原 満, 井関 健 日本薬学会年会要旨集 128年会 (4) 163 -163 2008年03月 [査読無し][通常論文]
  • 山崎 浩二郎, 西村 あや子, 宮本 剛典, 武隈 洋, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 18 245 -245 2008年
  • 植田 孝介, 武隈 洋, 沖 洋充, 須田 範行, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 18 253 -253 2008年
  • 清川 真美, 上野 あさひ, 池田 陽子, 須田 範行, 渡邊 昌也, 石川 康暢, 菅原 満, 武田 宏司, 井関 健 日本医療薬学会年会講演要旨集 18 262 -262 2008年
  • 熊井 正貴, 浅野 順次, 笠師 久美子, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 18 266 -266 2008年
  • Xin He, Mitsuru Sugawara, Xingbin Zhu, Shota Kadomura, Yang Wang, Yoh Takekuma, Changxiao Liu DRUG METABOLISM REVIEWS 40 31 -32 2008年 [査読無し][通常論文]
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    笠師 久美子, 柏崎 晴彦, 阿部 貴恵, 須田 範行, 菅原 満, 井関 健 静脈経腸栄養 23 (増刊) 213 -213 2008年01月 [査読無し][通常論文]
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  • 鷹野 瑠美, 平野 剛, 中田 千絵, 笠師 久美子, 菅原 満, 小林 正紀, 板垣 史郎, 井関 健, 大江 利治 日本医療薬学会年会講演要旨集 18 (0) 253 -253 2008年 [査読無し][通常論文]
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    清水 惠子, 松原 和夫, 菅原 満, 浅利 優, 丹 祐夏, 渡邊 智, 塩野 寛 中毒研究 20 (4) 438 -438 2007年10月
  • 斎藤由起子, 沖洋充, 平野剛, 菅原満, 井関健 日本医療薬学会年会講演要旨集 17th 315 -315 2007年09月01日 [査読無し][通常論文]
  • 落合 彰子, 小林 正紀, 板垣 史郎, 平野 剛, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 17 (0) 2007年09月01日 [査読無し][通常論文]
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    菅原 満, 唯野 貢司 TDM研究 24 (3) s56 -s57 2007年07月 [査読無し][通常論文]
  • テイコプラニンのローディングドーズがもたらす血中トラフ濃度と有効性の検討 中間報告
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  • 武隈 洋, 寺岡 栄美, 澤口 利香, 山崎 浩二郎, 森田 研, 下田 直彦, 堀田 記世彦, 岩見 大基, 渡井 至彦, 菅原 満, 野々村 克也, 井関 健 移植 42 (2) 194 -195 2007年04月 [査読無し][通常論文]
  • Pharmacokineticsの鑑定事例への応用 危険運転行為と覚せい剤摂取
    清水 惠子, 浅利 優, 安積 順一, 松原 和夫, 菅原 満, 塩野 寛 日本法医学雑誌 61 (1) 52 -52 2007年03月
  • ラット及びヒト間のMPA(ミコフェノール酸)体内動態の違いにおけるMRP2(multidrug resistance-associated protein 2)及びOAT(organic anion transporter)の関与
    垣内 悠, 武隈 洋, 山崎 浩二郎, 井関 健, 菅原 満 日本薬学会年会要旨集 127年会 (3) 84 -84 2007年03月 [査読無し][通常論文]
  • 川合 真次, 深井 敏隆, 荻野 修, 菅原 満, 櫻井 恒太郎, 井関 健 日本医療薬学会年会講演要旨集 17 206 -206 2007年
  • 西村 あや子, 坪内 孝敏, 山崎 浩二郎, 宮本 剛典, 武隈 洋, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 17 239 -239 2007年
  • 武隈 洋, 奥 健志, 小笠原 貴子, 山崎 浩二郎, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 17 240 -240 2007年
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  • 鷹野 瑠美, 須田 範行, 平野 剛, 笠師 久美子, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 17 (0) 223 -223 2007年 [査読無し][通常論文]
  • 副作用症状を来した肝移植患者における免疫抑制剤の選択
    小笠原貴子, 新沼朋美, 沖 洋充, 深井敏隆, 荻野 修, 武隈 洋, 菅原 満, 井関 健 北海道病院薬剤師会誌 72 35 -37 2007年 [査読無し][通常論文]
  • 久保田 康生, 中里 恭子, 須田 範行, 沖 洋充, 菅原 満, 小林 道也, 齊藤 浩司, 井関 健 日本医療薬学会年会講演要旨集 16 357 -357 2006年09月01日
  • 小笠原 貴子, 武隈 洋, 山崎 浩二郎, 沖 洋充, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 16 553 -553 2006年09月01日
  • 大西 潤, 井藤 達也, 志賀 隆博, 高木 智史, 鈴木 岳, 武隈 洋, 菅原 満, 竹本 功, 井関 健 日本医療薬学会年会講演要旨集 16 555 -555 2006年09月01日
  • 清川 真美, 澤口 利香, 須田 範行, 菅原 満, 井関 健 日本医療薬学会年会講演要旨集 16 320 -320 2006年09月01日
  • 井関健, 落合彰子, 黒川俊光, 板垣史郎, 平野剛, 菅原満 日本医療薬学会年会講演要旨集 16th 433 2006年09月01日 [査読無し][通常論文]
  • 菅原 満 TDM研究 23 (2) 55 -56 2006年04月 [査読無し][通常論文]
  • 武隈 洋, 武中 徹, 清川 真美, 山崎 浩二郎, 岡本 洋, 菅原 満, 北畠 顕, 筒井 裕之, 宮崎 勝巳 TDM研究 23 (2) 77 -78 2006年04月 [査読無し][通常論文]
  • 寺岡 栄美, 武隈 洋, 山崎 浩二郎, 高田 晴美, 菅原 満, 渡井 至彦, 森田 研, 福澤 信之, 野々村 克也, 宮崎 勝巳 TDM研究 23 (2) 145 -146 2006年04月 [査読無し][通常論文]
  • 注射オーダを利用した特定生物由来製剤の使用管理システム
    川合 真次, 山崎 浩二郎, 宮本 剛典, 荻野 修, 菅原 満, 井関 健, 櫻井 恒太郎 日本薬学会年会要旨集 126年会 (2) 220 -220 2006年03月 [査読無し][通常論文]
  • 國木 賢一, 山本 崇, 武隈 洋, 菅原 満, 井関 健 薬剤学: 生命とくすり 66 (Suppl.) 229 -229 2006年02月 [査読無し][通常論文]
  • 薬物療法時の血液浄化療法の影響 ~リネゾリド・ガンシクロビルについて~
    武隈 洋, 山﨑浩二郎, 宮本剛典, 菅原 満, 井関 健 第20回北海道TDM研究会(札幌) 2006年 [査読無し][通常論文]
  • 中性アミノ酸トランスポーターSNAT2の発現変動
    柏木 仁, 山﨑 浩二郎, 武隈 洋, 井関 健, 菅原 満 第20回北海道薬物作用談話会(札幌) 2006年 [査読無し][通常論文]
  • 血清アルブミンを中心としたMPA血中濃度の変動要因解析
    寺岡 栄美, 山﨑浩二郎, 菅原 満, 井関 健, 武隈 洋, 森田 研, 下田直彦, 堀田記世彦, 岩見大基, 渡井 至彦, 野々村克也 第24回北海道腎移植談話会(札幌) 2006年 [査読無し][通常論文]
  • 副作用症状を来した肝移植患者に対する免疫抑制剤の選択
    小笠原貴子, 新沼朋美, 武隈 洋, 沖 洋充, 深井敏隆, 荻野 修, 菅原 満, 井関 健 第53回北海道薬学大会(札幌) 2006年 [査読無し][通常論文]
  • 外来化学療法の取り組み 当院における外来治療センターの現状
    須田 範行, 荻野 修, 菅原 満, 井関 健 薬事新報 (2398) 9 -15 2005年12月 [査読無し][通常論文]
  • 久保田 康生, 沖 洋充, 菅原 満, 山崎 浩一, 西村 正治 日本医療薬学会年会講演要旨集 15 428 -428 2005年09月01日
  • 橋本 純一, 住吉 一宏, 川合 真次, 深井 敏隆, 荻野 修, 菅原 満, 櫻井 恒太郎, 宮崎 勝巳 日本医療薬学会年会講演要旨集 15 364 -364 2005年09月01日
  • 松浦 麻耶, 菅原 満, 篠原 信雄 泌尿器ケア 10 (9) 839 -843 2005年09月 [査読無し][通常論文]
  • 須田 範行, 菅原 満 新薬と臨牀 54 (8) 956 -963 2005年08月 [査読無し][通常論文]
     
    フルカリックは,初めて総合ビタミン剤を配合した高カロリー輸液キット製剤である.今回,1日容量製剤が開発され,有用性について,高カロリー輸液に適用されている処方を用いて検討した.A群(半日容量製剤2袋に薬剤を混注し,遮光タイプのIVHバッグ1袋に注入し1日分にまとめた群),B群(半日容量製剤2袋それぞれに薬剤を混注した群),C群(1日容量製剤1袋に薬剤を混注した群)とした.調剤順序は無作為に割付けを行った.調製時間はA群が640秒,B群が276秒,C群が224秒であった.C群はA群,B群と比較し有意に調製時間が短縮した.アンケート調査では,調製操作時間,調製操作の簡便性,利便性の総合評価の項目で有意差を認めた.半日容量製剤2袋を1日容量製剤1袋に変更可能な処方は97件あり,半日容量製剤194袋を1日容量製剤97袋に変更可能であった.フルカリック1日容量製剤は,臨床現場にとって有用性の高い製剤であることが示唆された
  • 山崎 浩二郎, 武隈 洋, 志賀 弘康, 菅原 満, 宮崎 勝巳, 小澤 剛久, 柴田 万里子, 橋本 聡一, 森本 裕二 TDM研究 22 (3) 238 -238 2005年07月 [査読無し][通常論文]
  • 井関 健, 板垣 史郎, 菅原 満, 宮崎 勝巳, 平野 剛 臨床薬理の進歩 (26) 20 -29 2005年07月 [査読無し][通常論文]
  • 武隈 洋, 清川 真美, 山崎 浩二郎, 米澤 一也, 岡本 洋, 菅原 満, 北畠 顕, 宮崎 勝巳 TDM研究 22 (2) 151 -152 2005年04月 [査読無し][通常論文]
  • ヌクレオシドトランスポーターを介した薬物輸送 CNTとENTの比較
    山本 崇, 國木 賢一, 武隈 洋, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 125年会 (2) 112 -112 2005年03月 [査読無し][通常論文]
  • 当院における外来治療センターの現状と問題点
    須田 範行, 瀬戸 恵介, 熊井 正貴, 岩井 美和子, 志賀 弘康, 宮本 剛典, 荻野 修, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 125年会 (2) 165 -165 2005年03月 [査読無し][通常論文]
  • 心疾患患者におけるカルベジロール薬物動態の母集団パラメータ解析
    武隈 洋, 清川 真美, 武中 徹, 山崎 浩二郎, 岡本 洋, 菅原 満, 北畠 顕, 筒井 裕之, 宮崎 勝巳 日本薬学会年会要旨集 125年会 (2) 181 -181 2005年03月 [査読無し][通常論文]
  • 救急・集中治療室12例におけるフレカイニド静注薬の効果解析
    松田直之, 大城あき子, 下嶋秀和, 久保田信彦, 星野弘勝, 早川峰司, 澤村 淳, 石川岳彦, 丸藤 哲, 武隈 洋, 菅原 満 第6回抗不整脈薬TDM研究会(東京) 2005年 [査読無し][通常論文]
  • 神経因性疼痛に対する酢酸フレカイニドの鎮痛効果の検討
    武隈 洋, 山﨑浩二郎, 志賀弘康, 菅原 満, 宮崎勝巳, 小澤剛久, 柴田万里子, 橋本聡一, 森本裕二 第6回抗不整脈薬TDM研究会(東京) 2005年 [査読無し][通常論文]
  • 総合ビタミン剤配合型高カロリー輸液キット製剤「フルカリック®」1日容量製剤の有用性の検討
    須田範行, 菅原 満 新薬と臨床 54 (8) 18 -25 2005年 [査読無し][通常論文]
  • 【日常診療に用いられる薬剤の上手な使い方と服薬指導】薬物の吸収とその変動要因
    菅原 満, 宮崎 勝巳 成人病と生活習慣病 35 (1) 9 -16 2005年01月 [査読無し][通常論文]
     
    経口投与製剤は,その服用しやすさからもっとも汎用される剤形であるが,薬理作用が消化管からの吸収性の変動により影響を受けることが多々ある.薬物の消化管からの吸収に変動を及ぼす生理的要因や,食事や併用薬との相互作用として,(1)消化管運動の亢進・抑制,(2)複合体形成および吸着,(3)消化管内pHの変動,(4)代謝酵素阻害・誘導,(5)トランスポーターの阻害・誘導,(6)腸内細菌叢の変化などがある.これらの要因による薬理効果の変動や副作用の発現を防ぐために,薬剤師による処方監査やコンピュータシステムによる処方チェック,さらには患者への服薬指導が重要な役割を果たす.薬物の消化管吸収における相互作用が生じる組み合わせが入力された時に,相互作用の内容とともに,薬剤を変更する際の代替薬の提示や対処法を併せてコメントとして表示するコンピュータシステムの導入,あるいは薬効や副作用とともに,使用上の注意を記載した情報提供用紙は非常に有用である.副作用や相互作用は,事前の知識によりある程度回避することができる.そのためには,患者や周囲にいる人がその初期症状に気づき,早急に対処することも重要である.薬効や副作用とともに,このような使用上の注意を,専門用語を用いずにわかりやすい表現で記載した情報提供用紙が服薬指導には欠かせない(著者抄録)
  • 坪井 瞳, 板垣 まゆこ, 今田 愛也, 阿部 康子, 金重 啓子, 樟本 賢首, 岸野 吏志, 菅原 満, 宮崎 勝巳 TDM研究 21 (4) 336 -336 2004年10月
  • 【Q&Aで学ぶTDM活用ガイド】TDMを始める準備をする TDMを始める前に知っておきたいこと 特定薬剤治療管理料の算定は薬剤によって異なるそうですね.ややこしいので教えてください
    菅原 満, 宮崎 勝巳 薬局 55 (10月臨増) 6 -7 2004年10月 [査読無し][通常論文]
  • 【Q&Aで学ぶTDM活用ガイド】TDMを始める準備をする TDMを始める前に知っておきたいこと TDMを実施すると経済的なメリットはあるのでしょうか?
    菅原 満, 宮崎 勝巳 薬局 55 (10月臨増) 8 -10 2004年10月 [査読無し][通常論文]
  • 【Q&Aで学ぶTDM活用ガイド】TDMを始める準備をする TDMを始める前に知っておきたいこと 血中濃度は常に有効治療域に入れなければならないのでしょうか?
    菅原 満, 宮崎 勝巳 薬局 55 (10月臨増) 11 -13 2004年10月 [査読無し][通常論文]
  • 須田 範行, 新里 利香, 清川 真美, 金内 美妃, 菅原 満, 郡 修徳, 宮崎 勝巳 日本医療薬学会年会講演要旨集 14 268 -268 2004年09月01日
  • 志賀 弘康, 川合 真次, 荻野 修, 菅原 満, 宮崎 勝巳 日本医療薬学会年会講演要旨集 14 274 -274 2004年09月01日
  • 北海道大学病院における治験実施体制の整備と新たな取り組み
    後藤 瑞子, 橋本 あきら, 荻野 修, 菅原 満, 宮崎 勝巳, 亀田 悦子, 奥原 芳子, 河野 敏春, 佐藤 典宏, 遠藤 晃, 櫻井 恒太郎, 小池 隆夫 臨床薬理 35 (Suppl.) S201 -S201 2004年08月 [査読無し][通常論文]
  • 岸野 吏志, 馬渕 朋美, 菅原 満, 嶋村 剛, 古川 裕之, 藤堂 省, 宮崎 勝巳 TDM研究 21 (2) 145 -146 2004年04月 [査読無し][通常論文]
  • 井上 直樹, 岡本 洋, 福島 新, 本間 恒章, 小松 博史, 長嶋 健一郎, 秋野 正敏, 松井 裕, 小野塚 久夫, 米澤 一也, 北畠 顕, 菅原 満, 東 純一 Circulation Journal 68 (Suppl.II) 758 -758 2004年04月 [査読無し][通常論文]
  • 菅原 満, 宮崎 勝巳 医薬ジャ-ナル 40 (3) 130 -136 2004年03月
  • 肝のう胞治療時のジソピラミド血中濃度モニタリング エタノール注入療法患者の症例
    坪井 瞳, 板垣 まゆ子, 今田 愛也, 金重 啓子, 樟本 賢首, 岸野 吏志, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 124年会 (4) 184 -184 2004年03月
  • AAG variantに対するクロルプロマジンの結合に及ぼすシアル酸の影響
    中川 勉, 佐々木 花, 武隈 洋, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 124年会 (4) 87 -87 2004年03月 [査読無し][通常論文]
  • タキソール注投与時の結晶析出に関する報告
    岩井 美和子, 須田 範行, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 124年会 (4) 125 -125 2004年03月 [査読無し][通常論文]
  • 癌化学療法の調剤業務支援のためのプロトコールデータベースの構築と運用
    武隈 洋, 岩井 美和子, 藤原 俊恵, 川岸 亨, 熊井 正貴, 松浦 麻耶, 前佛 美也子, 高橋 悠子, 相楽 賢一, 馬渕 朋美, 須田 範行, 宮本 剛典, 荻野 修, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 124年会 (4) 150 -150 2004年03月 [査読無し][通常論文]
  • hOAT1を介した有機アニオン輸送に対するキサンチン系薬物の阻害効果
    菅原 満, 望月 敬浩, 武隈 洋, 宮崎 勝巳 日本薬学会年会要旨集 124年会 (4) 76 -76 2004年03月 [査読無し][通常論文]
  • 板垣 史郎, 菅原 満, 小林 道也, 平野 剛, 宮崎 勝巳, 井関 健 日本薬学会年会要旨集 124年会 (4) 75 -75 2004年03月 [査読無し][通常論文]
  • 菅原 満, 宮崎 勝巳 薬局 55 (3) 1481 -1490 2004年03月 [査読無し][通常論文]
  • 菅原 満, 宮崎 勝巳 医薬ジャーナル 40 (3) 1012 -1018 2004年03月 [査読無し][通常論文]
     
    薬剤師による処方支援の例として,病棟活動を通じて薬剤師が処方計画に参画できたケースについて,北海道大学病院において経験した例を紹介する.一方,病棟活動を行っていない診療科においても,何らかの形で処方を支援する方策が必要である.そこで,薬剤部において作成したデータベースを,処方オーダリングシステムにリンクすることにより,処方作成を支援する取り組みについても述べた
  • T Nakagawa, S Kishino, S Itoh, M Sugawara, K Miyazaki BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 57 (2) 226 -226 2004年02月 [査読無し][通常論文]
  • 拡張型心筋症患者におけるβ遮断薬薬剤反応性と遺伝子多型性解析
    岡本 洋, 小野塚 久夫, 米澤 一也, 北畠 顕, 菅原 満, 東 純一 日本内科学会雑誌 93 (Suppl.) 170 -170 2004年02月 [査読無し][通常論文]
  • 急性腎不全患者におけるフレカイニドの血中濃度と頻脈抑制作用の一例
    松田直之, 平安山直美, 早川峰司, 澤村 淳, 亀山 隆, 丸藤 哲, 武隈 洋, 菅原 満, 宮崎勝巳 第5回抗不整脈薬TDM研究会(福岡) 2004年 [査読無し][通常論文]
  • hOAT1の基質認識における構造相関~核酸類似構造化合物を用いた検討~
    小田真也, 望月敬浩, 武隈 洋, 菅原 満, 宮崎勝巳 日本薬学会北海道支部第122回例会(札幌) 2004年 [査読無し][通常論文]
  • 奥村勝彦監修、Q&Aで学ぶTDM活用ガイド
    菅原 満, 宮崎勝巳 薬局 55 (10月臨時増刊号) 6 -13 2004年 [査読無し][通常論文]
  • 清川 真美, 武隈 洋, 岸野 吏志, 深井 敏隆, 高木 眞弓, 米澤 一也, 菅原 満, 宮崎 勝巳, 北畠 顯 日本医療薬学会年会講演要旨集 13 132 -132 2003年09月01日
  • 抗がん剤適正使用を支える医薬品プロフィール
    政田 幹夫, 菅原 満, 有吉 範高, 森田 邦彦, 川上 純一, 後藤 伸之, 中村 敏明, 栄田 敏之, 直良 浩司, 井関 健, 黒崎 勇二, 谷川原 祐介, 向山 雄人 日本癌治療学会誌 38 (2) 202 -202 2003年09月
  • 岡本 洋, 秋野 正敏, 松井 裕, 米澤 一也, 小野塚 久夫, 北畠 顕, 菅原 満, 東 純一 日本内分泌学会雑誌 79 (2) 539 -539 2003年09月 [査読無し][通常論文]
  • 岸野 吏志, 馬渕 朋美, 菅原 満, 嶋村 剛, 古川 裕之, 藤堂 省, 宮崎 勝巳 TDM研究 20 (2) 183 -184 2003年04月 [査読無し][通常論文]
  • 岸野 吏志, 菅原 満, 古川 博之, 藤堂 省, 宮崎 勝巳 日本外科学会雑誌 104 (臨増) 434 -434 2003年04月 [査読無し][通常論文]
  • システムB0を介した中性アミノ酸の輸送におよぼす塩基性薬物の影響
    北窪 真弓, 武隈 洋, 菅原 満, Ganapathy V., 宮崎 勝巳 日本薬学会年会要旨集 123年会 (4) 61 -61 2003年03月 [査読無し][通常論文]
  • α1-酸性糖蛋白質への立体選択的な薬物結合におけるシアル酸の影響
    中川 勉, 伊藤 慎, 岸野 吏志, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 123年会 (4) 69 -69 2003年03月 [査読無し][通常論文]
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    何 新, 武隈 洋, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 123年会 (4) 101 -101 2003年03月 [査読無し][通常論文]
  • 癌化学療法時の口内炎予防を目的としたメシル酸カモスタット口腔内速崩錠の調製とその評価
    須田 範行, 今野 安大, 岩井 美和子, 森田 豊, 中田 宏, 菅原 満, 宮崎 正三, 宮崎 勝巳 日本薬学会年会要旨集 123年会 (4) 122 -122 2003年03月 [査読無し][通常論文]
  • カルニチントランスポーター(OCTN2)発現細胞を用いた基質認識特性の解明
    高野太樹, 武隈 洋, 菅原 満, 宮崎勝巳 日本薬学会北海道支部第120回例会(札幌) 2003年 [査読無し][通常論文]
  • システムAアミノ酸トランスポーターの活性・発現におよぼすインスリンの影響
    柏木 仁, 武隈 洋, 菅原 満, 宮崎勝巳 日本薬学会北海道支部第120回例会(札幌) 2003年 [査読無し][通常論文]
  • 抗ウイルス薬リバビリンの胎盤透過機構
    森田 崇, 武隈 洋, 菅原 満, 宮崎勝巳 日本薬学会北海道支部第120回例会(札幌) 2003年 [査読無し][通常論文]
  • フェンタニルパッチ連日投与により傾眠が改善された一症例
    志賀弘康, 荻野 修, 菅原 満, 宮崎勝巳 北海道病院薬剤師会誌 65 37 -40 2003年 [査読無し][通常論文]
  • リスク軽減を目的とした調剤業務のシステム化−薬袋作製機の導入−
    橋本純一, 深井敏隆, 荻野 修, 菅原 満, 宮崎勝巳 北海道病院薬剤師会誌 64 53 -56 2003年 [査読無し][通常論文]
  • 菅原 満 日本医療薬学会会報 6 (4) 16 -25 2002年12月 [査読無し][通常論文]
  • 橋本 純一, 山下 恭範, 榊原 則寛, 川合 真次, 深井 敏隆, 荻野 修, 菅原 満, 宮崎 勝巳 日本医療薬学会年会講演要旨集 12 156 -156 2002年09月24日
  • 岸野 吏志, 小川 真紀, 菅原 満, 古川 博之, 藤堂 省, 宮崎 勝巳 日本医療薬学会年会講演要旨集 12 253 -253 2002年09月24日
  • 病院における製剤 くる病患者のリン酸補給に対するリン酸バッファー錠の調整と臨在学的評価
    岸野 吏志, 菅原 満, 宮崎 勝巳, 郡 修徳 PHARM TECH JAPAN 18 (8) 1227 -1233 2002年07月 [査読無し][通常論文]
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    菅原 満 日本薬学会年会要旨集 122年会 (1) 195 -195 2002年03月 [査読無し][通常論文]
  • 消化管内pH変動および腸管代謝を考慮した薬物吸収予測システムの構築
    何 新, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (4) 51 -51 2002年03月 [査読無し][通常論文]
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    瀬戸 恵介, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (4) 63 -63 2002年03月 [査読無し][通常論文]
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    伊藤 慎, 中川 勉, 岸野 吏志, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (4) 71 -71 2002年03月 [査読無し][通常論文]
  • α1-酸性糖蛋白質とその不均一性体の糖鎖構造解析
    中川 勉, 越浪 由加, 佐々木 花, 岸野 吏志, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (4) 71 -71 2002年03月 [査読無し][通常論文]
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    岸野 吏志, 菅原 満, 宮崎 勝巳, 古川 博之, 藤堂 省 日本薬学会年会要旨集 122年会 (4) 124 -124 2002年03月 [査読無し][通常論文]
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    菅原 満, 荻野 修, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (4) 149 -149 2002年03月 [査読無し][通常論文]
  • 川合 真次, 平野 剛, 菅原 満, 井関 健, 岸野 吏志, 荻野 修, 野村 靖幸, 宮崎 勝巳 日本薬学会年会要旨集 122年会 (3) 203 -203 2002年03月 [査読無し][通常論文]
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    高田陽美, 橋本あきら, 荻野 修, 菅原 満, 宮崎勝巳, 竹内ひとみ, 奥原芳子, 小柳知彦 北海道病院薬剤師会誌 62 63 -68 2002年 [査読無し][通常論文]
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    久保田康生, 深井敏隆, 荻野 修, 菅原 満, 宮崎勝巳 北海道病院薬剤師会誌 62 35 -38 2002年 [査読無し][通常論文]
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    菅原 満, 宮崎 勝巳 医薬ジャーナル 38 (増刊) 342 -346 2002年01月 [査読無し][通常論文]
  • 清川 真美, 岸野 吏志, 深井 敏隆, 高木 眞弓, 米澤 一也, 小林 道也, 菅原 満, 宮崎 勝巳, 北畠 顯 日本医療薬学会年会講演要旨集 11 94 -94 2001年09月01日
  • 岩井 美和子, 武隈 洋, 須田 範行, 岸野 吏志, 菅原 満, 古川 博之, 藤堂 省, 宮崎 勝巳 日本医療薬学会年会講演要旨集 11 134 -134 2001年09月01日
  • 山崎 浩二郎, 北窪 真弓, 小林 道也, 菅原 満, 宮崎 勝巳 薬物動態 16 (Suppl.) S309 -S309 2001年09月 [査読無し][通常論文]
  • 板垣 史郎, 小林 道也, 井関 健, 菅原 満, 宮崎 勝巳 薬物動態 16 (Suppl.) S243 -S243 2001年09月 [査読無し][通常論文]
  • 菅原 満 ファルマシア 37 (7) 657 -658 2001年07月 [査読無し][通常論文]
  • C6 glioma細胞におけるsystem Aアミノ酸トランスポーターの機能特性
    田中 一成, 杉浦 香織, 藤川 世梨, 岡田 直貴, 藤田 卓也, 山本 昌, 菅原 満, Leibach Frederick H., Ganapathy Vadivel 日本薬学会年会要旨集 121年会 (3) 83 -83 2001年03月
  • アミノ酸輸送担体システムAのクローニング及び機能解析
    菅原 満, Leibach Frederick H., Ganapathy Vadivel, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 83 -83 2001年03月 [査読無し][通常論文]
  • α1-酸性糖蛋白質とその不均一性体に対する光学異性体薬物の立体選択的結合性
    中川 勉, 伊藤 慎, 岸野 吏志, 小林 道也, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 95 -95 2001年03月 [査読無し][通常論文]
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    岩井 美和子, 志賀 弘康, 山下 恭範, 須田 範行, 武隈 洋, 岸野 吏志, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 139 -139 2001年03月 [査読無し][通常論文]
  • 生体肝移植患者におけるタクロリムスの体内動態(2)
    岸野 吏志, 志賀 弘康, 山下 恭範, 岩井 美和子, 菅原 満, 古川 博之, 藤堂 省, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 141 -141 2001年03月 [査読無し][通常論文]
  • 高アンモニア血症に対する院内製剤供給後の治療成績評価
    山下 恭範, 岩井 美和子, 志賀 弘康, 岸野 吏志, 菅原 満, 宮崎 勝巳, 窪田 満, 小林 邦彦 日本薬学会年会要旨集 121年会 (3) 139 -139 2001年03月 [査読無し][通常論文]
  • 薬剤師主導による心不全患者に対するカルベジロール投与プロトコールの構築
    清川 真美, 岸野 吏志, 深井 敏隆, 高木 眞弓, 米澤 一也, 小林 道也, 菅原 満, 宮崎 勝巳, 北畠 顯 日本薬学会年会要旨集 121年会 (3) 177 -177 2001年03月 [査読無し][通常論文]
  • 北大病院における治験コーディネーター業務への取り組み
    橋本 あきら, 高田 陽美, 川合 真次, 荻野 修, 菅原 満, 浅野 弘恵, 木下 克恵, 竹内 ひとみ, 奥原 芳子, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 157 -157 2001年03月 [査読無し][通常論文]
  • 消化管内pH変動を考慮した薬物吸収評価系の改良と消化管内薬物相互作用の評価
    小林 道也, 佐田 憲昭, 立浪 綾子, 坪井 瞳, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 110 -110 2001年03月 [査読無し][通常論文]
  • 病棟業務における薬剤師の職能 循環器科病棟におけるプレアボイド症例
    沖 洋充, 清川 真美, 深井 敏隆, 小林 道也, 荻野 修, 菅原 満, 宮崎 勝巳 日本薬学会年会要旨集 121年会 (3) 163 -163 2001年03月 [査読無し][通常論文]
  • グルタミントランスポーターの機能解析
    菅原 満 日本薬剤学会会報”生命とくすり” 17 (4) 6 -7 2001年 [査読無し][通常論文]
  • 各種イオン型薬物の小腸基底膜透過に及ぼす膜電位の影響
    小林 道也, 吉田 英人, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 15 (Suppl.) S278 -S278 2000年09月 [査読無し][通常論文]
  • 消化管内pH変動を考慮した吸収評価系によるヒト薬物動態予測
    佐田 憲昭, 菅原 満, 小林 道也, 中 正道, 井関 健, 宮崎 勝巳 薬物動態 15 (Suppl.) S278 -S278 2000年09月 [査読無し][通常論文]
  • 井藤 達也, 秦 温信, 高岡 和夫, 藤崎 博子, 菅原 満, 井関 健, 宮崎 勝巳 TDM研究 17 (2) 121 -122 2000年04月
  • 薬物の生体内動態における構造相関(第49報) 消化管内pHの変動を考慮した難溶性薬物の消化管吸収評価法
    佐田 憲昭, 菅原 満, 小林 道也, 中 正道, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 120年会 (4) 51 -51 2000年03月 [査読無し][通常論文]
  • ヒト小腸及びCaco-2細胞を用いた薬物吸収性評価 P-glycoproteinによる排出系の異同性
    早川 智久, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 14 (Suppl.) S170 -S170 1999年09月 [査読無し][通常論文]
  • 消化管内pHの変動を考慮した薬物の消化管吸収評価法の確立
    佐田 憲昭, 菅原 満, 小林 道也, 中 正道, 井関 健, 宮崎 勝巳 薬物動態 14 (Suppl.) S217 -S217 1999年09月 [査読無し][通常論文]
  • 高速液体クロマトグラフィーによる血清中ピルジカイニド定量法の確立
    井藤 達也, 新庄 一, 尾形 仁子, 中川 英久, 浜辺 晃, 菅原 満, 井関 健, 宮崎 勝巳 Journal of Cardiology 34 (Suppl.I) 308 -308 1999年08月
  • 井藤 達也, 福島 紘司, 尾形 仁子, 中川 英久, 浜辺 晃, 菅原 満, 井関 健, 宮崎 勝巳 TDM研究 16 (2) 149 -150 1999年04月
  • 胃癌患者における胃切除術後の薬物吸収動態
    井藤 達也, 福田 由布子, 福島 紘司, 真鍋 邦彦, 秦 温信, 佐野 文男, 斎藤 正信, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 119年会 (4) 146 -146 1999年03月
  • 薬物の生体内動態における構造相関(第48報) 多剤排出蛋白を介したPSP(Phenolsulfonphthalein)の腎排泄
    小林 道也, 藤本 道夫, 西村 幸穂, 井上 悟, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 119年会 (4) 9 -9 1999年03月 [査読無し][通常論文]
  • イオン型薬物の消化管吸収に及ぼす膜表面電位の影響
    黒澤 恵, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 13 (Suppl.) S219 -S219 1998年10月 [査読無し][通常論文]
  • ラット小腸H+依存性輸送タンパクの精製とその機能評価
    神谷 あや子, 小林 道也, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 13 (Suppl.) S268 -S268 1998年10月 [査読無し][通常論文]
  • 小林 道也, 深井 敏隆, 岸野 吏志, 川合 真次, 菅原 満, 宮本 剛典, 荻野 修, 井関 健, 宮崎 勝巳 日本病院薬学会年会講演要旨集 8 90 -90 1998年08月17日
  • 井関 健, 浅子 恵, 金内 美妃, 菅原 満, 宮崎 勝巳 薬剤学 58 150 -150 1998年03月05日
  • 薬物の生体内動態における構造相関(第43報) LECラットにおけるフェノールスルホンフタレインの腎排泄挙動
    藤本 道夫, 小林 道也, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 118年会 (4) 36 -36 1998年03月 [査読無し][通常論文]
  • 高アンモニア血症治療薬フェニル酢酸製剤の生体内動態
    馬渕 朋美, 板垣 文雄, 橋本 あきら, 岸野 吏志, 菅原 満, 井関 健, 宮崎 勝巳, 郡 修徳, 長坂 博範, 窪田 満 日本薬学会年会要旨集 118年会 (4) 150 -150 1998年03月 [査読無し][通常論文]
  • 薬物の生体内動態における構造相関(第42報) トリエンチンの尿中排泄におけるスペルミン輸送担体の寄与
    藤崎 博子, 小林 道也, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 118年会 (4) 36 -36 1998年03月 [査読無し][通常論文]
  • 薬物の生体内動態における構造相関(第44報) 難水溶性薬物の消化管吸収予測
    菅原 満, 古居 奈歩, 小林 道也, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 118年会 (4) 7 -7 1998年03月 [査読無し][通常論文]
  • 薬物の生体内動態における構造相関(第45報) 薬物の消化管吸収に及ぼす膜表面電位の影響
    黒澤 恵, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 118年会 (4) 7 -7 1998年03月 [査読無し][通常論文]
  • 最近の文献情報より 薬物相互作用に関する文献情報(6)
    小林道也, 平野 剛, 菅原 満, 宮崎勝巳 日病薬誌 34 1559 -1561 1998年 [査読無し][通常論文]
  • 最近の文献情報より 薬物相互作用に関する文献情報(4)
    菅原 満, 岸野吏志, 小林道也, 宮崎勝巳 日病薬誌 34 969 -971 1998年 [査読無し][通常論文]
  • 最近の文献情報より 薬物相互作用に関する文献情報(3)
    平野 剛, 菅原 満, 岸野吏志, 宮崎勝巳 日病薬誌 34 669 -671 1998年 [査読無し][通常論文]
  • 最近の文献情報より 薬物相互作用に関する文献情報(2)
    平野 剛, 小林道也, 菅原 満, 宮崎勝巳 日病薬誌 34 347 -349 1998年 [査読無し][通常論文]
  • 米村 一洋, 神谷 あや子, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 = Xenobiotic metabolism and disposition 12 195 -195 1997年10月09日
  • 薬物の生体内動態における構造相関(第40報) 物理化学的測定値を用いた薬物の消化管吸収予測式の構築
    菅原 満 日本薬学会年会要旨集 117年会 (4) 13 -13 1997年03月 [査読無し][通常論文]
  • 小林 道也, 藤崎 博子, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 12 76 -77 1997年 
    The mechanism of renal excretion of polyamine drugs has been investigated in vivo and in vitro. Trientine clearance (CLtri) in the rat was significantly faster than creatinine clearance (CLcr). However, CLtri decreased to almost the same level as the CLcr when trientine and the same number of moles of copper ions were administered simultaneously to the rat. To clarify this active excretion system for trientine, the uptake of trientine and spermine, a physiological polyamine, was investigated using the rat renal proximal tubular brush-border membrane vesicles (BBMV). An outwardly directed Na+ gradient remarkably enhanced the uptake of these polyamine compounds, however, it did not affect the uptake of trientine-Cu complex. The Na+-dependent uptake of [3H]spermine was completely inhibited by spermine, trientine and tetraethylenepentamine. On the contrary, physiological polyamines (putrescine and spermidine) which have 2 or 3 amino-groups, and aminoglycoside antibiotics which have 4 or 5 cationic amines, did not affect the uptake of spermine in the presence of an outward Na+ gradient. These results suggest that the mechanism contribute to the renal tubular secretion of spermine is a Na+/spermine antiport system, and this transporter recognizes the straight-chain polyamine drug which has more than 4 amino-groups in its molecule.
  • 加藤 雅也, 菅原 満, 小林 道也, 井関 健, 宮崎 勝巳 薬物動態 12 74 -75 1997年 
    We investigated the effect of cationic drugs on carrier mediated transport using in vitro and in situ techniques. The initial uptake of glucose, alanine and glutamic acid by rat intestinal brush border membrane vesicles(BBMV) was distinctly inhibited by imipramine in the presence of Na+ gradient, but not inhibited in the absence of Na+ gradient. This result indicates that imipramine inhibited carrier mediated transport. Imipramine exhibited competitive inhibition with respect to Na+ concentration, while exhibited non-competitive inhibition with respect to glutamic acid concentration. This finding suggests that imipramine affected carrier mediated transport by competitive inhibition to Na+ binding site of the carrier. On the other hand, in situ single pass perfusion method showed that absorption of alanine was also inhibited by imipramine and other cationic drugs in the presence of Na+, but not inhibited in the absence of Na+. This result is agreement with that of BBMV study. The inhibition of carrier mediated alanine transport by cationic drugs in BBMV corresponded to that in situ. There was a relatively good correlationship between the BBMV study and in situ perfusion study in the inhibitory effects.
  • 武隈 洋, 菅原 満, 山田 晴美, 小林 道也, 井関 健, 宮崎 勝巳 薬物動態 = Xenobiotic metabolism and disposition 11 S108 -S109 1996年09月20日 
    A predicting method for the intestinal absorption of drugs by measuring their physicochemical properties such as organic solvent / buffer partition coefficient, molecular volume (molecular weight), hydrogen bonding and diffusion rate across silicone membrane was investigated. A poor correlation was observed between absorption rate from intestinal lumen and organic solvent / buffer partition coefficient of tested drugs. On the contrary, good regression coefficient (R = 0.801) was obtained when the three factors (molecular weight, hydrogen bonding, and permeation rate across silicone membrane) were used. On the other hand, the excellent regression was observed when the drugs were classified into anionic, cationic, and neutral groups. These results suggest that the permeation rate across silicone membrane, molecular weight, and hydrogen bonding are valuable measures for predicting the absorption behavior of drugs. Moreover, an additional parameter which reflects the effect of the molecular charge will be necessary.
  • 薬物の生体内動態における構造相関(第36報) グルタミン酸の小腸刷子縁膜透過に及ぼすカチオン型薬物の影響
    菅原 満, 加藤 雅也, 小林 道也, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 116年会 (4) 38 -38 1996年03月
  • 薬物の生体内動態における構造相関(第34報) ポリアミン類のラット腎刷子縁膜透過機構
    小林 道也, 田辺 亮, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 116年会 (4) 46 -46 1996年03月
  • 薬物の生体内動態における構造相関(第35報) ラット腎セフチブテン輸送担体の再構成
    菊地 崇行, Naasani Imad, 菅原 満, 井関 健, 宮崎 勝巳 日本薬学会年会要旨集 116年会 (4) 46 -46 1996年03月
  • 菅原 満 薬物動態 10 (Suppl.) 317 -317 1995年10月 [査読無し][通常論文]
  • 辻華里, 平野剛, 宮崎正三, 高田昌彦, 菅原満, 井関健, 宮崎勝巳 日本薬学会年会要旨集 115th (Pt 4) 102 1995年03月 [査読無し][通常論文]
  • 菅原 満 薬物動態 9 (Suppl.) 62 -65 1994年10月 [査読無し][通常論文]
  • 平野剛, 宮崎正三, 高田昌彦, 菅原満, 井関健, 宮崎勝巳 薬物動態 9 (Suppl) S110-S113 1994年10月 [査読無し][通常論文]
  • TAKAHASHI YASUSHI, ITOH TATSUYA, KOBAYASHI MICHIYA, SUGAWARA MITSURU, SAITOH HIROSHI, ISEKI KEN, MIYAZAKI KATSUMI, MIYAZAKI SHOZO, TAKADA MASAHIKO, KAWASHIMA YOSHIAKI 岐阜藥科大學紀要 43 84 -84 1994年06月30日
  • 菅原 満, 小林 道也, 井関 健, 宮崎 勝巳 薬物動態 9 62 -65 1994年 
    The effect of membrane surface potential on the permeation of ionic compounds through the intestinal brush-border membrane was investigated using uptake experiments by brush-border membrane vesicles (BBMV) and large unilamellar vesicles (LUV). The uptake of anionic compounds (ceftibuten, cefixime, benzylpenicillin etc.) was decreased with increase of membrane surface negativity. On the other hand, the uptake of a cationic compound, tryptamine, was increased with increase of surface negativity. The uptake of these ionic compounds was well correlated with membrane surface potential of BBMV and LUV monitored by ANS. These results suggest that the permeation of ionic compounds through the intestinal brush-border membrane is dependent on the membrane surface potential. The mechanism of inhibitory effect on the uptake among these Ionic compounds was also examined from the viewpoint of changes in the membrane surface potential. The inhibitory effect of tetracaine and imipramine on the uptake of tryptamine was well correlated with changes in the membrane surface potential induced by these organic cations. Similar relation was observed in the inhibitory effect of flufenamic acid on the uptake of cefixime. These results suggest that changes in the membrane surface potential contribute to the inhibitory effect on the uptake of these Ionic compounds.
  • 小林 道也, 菅原 満, 井関 健, 宮崎 勝巳 薬物動態 8 743 -746 1993年 
    The uptake characteristics of polyamines have been investigated using rat intestinal brush-border membrane vesicles (BBMV). The uptake of these polyamines into BBMV was high and the order of uptake activity was spermine > spermidine > putrescine, and the medium pH affected remarkably the uptake of polyamines (pH 7.5 > pH 5.5). We have also examined the binding behavior of polyamines to liposome, and the similar phenomenon such as uptake activity and pH-dependency was observed. An inward Na+ gradient did not stimulate the initial uptake of all polyamines. The uptake rate of spermine and spermidine were saturable (Km = 30.4 and 148.1 μM, respectively), but putrescine was not saturable up to 8 mM. Spermine competitively inhibited the uptake rate of spermidine (Ki = 33.8 NM), while putrescine inhibited spermidine non-competitively (Ki = 3.28 mM). However, intravesicular spermine exhibited no trans-stimulation effect on the uptake of spermine and spermidine. Therefore, the polyamines were considered to be taken up via a passive diffusion mechanism rather than the carrier-mediated systems. The interaction between polyamine and inner-layer acidic phospholipids of BBMV might play an important role as a driving force of the polyamine uptake mechanism. Furthermore, the uptake mechanism of polyamine was different from cationic compounds because valinomycin-induced potassium diffusion potential (inside negative) did not affect the uptake of polyamines.
  • 薬物の生体内動態における構造相関(第1報) β-ラクタム系抗生物質の消化管吸収機構
    菅原 満 日本薬学会年会要旨集 111年会 (4) 137 -137 1991年03月 [査読無し][通常論文]
  • βラクタム系抗生物質の小腸刷子縁膜透過性
    菅原 満 日本薬学会年会要旨集 109年会 (2) 76 -76 1989年03月 [査読無し][通常論文]

教育活動情報

主要な担当授業

  • 生命医薬科学概論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 生命科学院
    キーワード : (生命医薬科学概論) 有機合成化学,天然物化学,神経,免疫,蛋白質,脂質,遺伝子解析,RNA,バイオイメージング解析,薬剤吸収,薬物送達,痛み,立体構造 (生命融合科学概論/ソフトマター科学概論) 生命融合科学,生命情報分子科学,生命物質科学,細胞機能科学,生命機能制御科学,ソフトマター科学,ソフトマター材料科学,ソフトマター生命分子科学,ソフトマター生体物理学,ソフトマター医科学,SDGs (生命システム科学概論) 細胞増殖,細胞極性,細胞分化,形態形成,遺伝子発現,植物免疫,神経回路,動物行動学,能科学,生殖機構,発生,内分泌,ホルモン,オムニバス,現代生命科学,知的財産
  • 臨床薬学実習
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 生命科学院
    キーワード : 薬学的病棟管理、臨床研究、 専門薬剤師認定、 臨床治験
  • 医療疫学特論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 生命科学院
    キーワード : 疫学,研究デザイン
  • 臨床研究計画法
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 生命科学院
    キーワード : 臨床薬理学、治験、評価項目、バイオマーカー、生物統計学
  • 薬物治療学特論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 生命科学院
    キーワード : 代謝、免疫、感染症、がん、個別化医療、分子標的、分子マーカー 標準的薬物治療、治療ガイドライン、 リスクマネジメント、 医薬品適正使用、医薬品相互作用 消化管吸収,薬物代謝,腎排泄,TDM
  • 薬局実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 薬学実務実習
  • 薬剤学Ⅲ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 日本薬局方,製剤
  • 医薬品安全性学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 有害事象,副作用,中毒
  • 病院薬局管理論
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 病院薬剤部、医薬品安全管理、病棟業務、セーフティマネジメント, 社会貢献活動
  • 臨床薬剤学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : チーム医療,医療安全,服薬指導,TDM
  • 薬物代謝学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 薬物代謝,個体差,相互作用
  • 病院実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 病院,実務実習

大学運営

委員歴

  • 2019年12月 - 現在   日本臨床薬理学会   代議員
  • 2014年04月 - 現在   日本TDM学会   理事
  • 2004年 - 現在   日本TDM学会   評議員   日本TDM学会
  • 2002年 - 現在   日本医療薬学会   代議員   日本医療薬学会
  • 2019年06月   医薬品相互作用研究会   理事


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