研究者データベース

武隈 洋(タケクマ ヨウ)
北海道大学病院 薬剤部
准教授

基本情報

所属

  • 北海道大学病院 薬剤部

職名

  • 准教授

学位

  • 博士(薬学)(北海道大学)

J-Global ID

研究キーワード

  • 生物系薬学   医療系薬学   

研究分野

  • ライフサイエンス / 薬理学
  • ライフサイエンス / 薬系衛生、生物化学
  • ライフサイエンス / 医療薬学

所属学協会

  • 日本化学療法学会   日本薬剤疫学会   医薬品相互作用研究会   日本臨床疫学会   日本薬局学会   International Association of Therapeutic Drug Monitoring and Clinical Toxicology   日本医薬品情報学会   日本TDM学会   日本医療薬学会   日本薬学会   日本薬物動態学会   北海道TDM研究会   Japanese Society of Drug Informatics   The Japanese Society of Therapeutic Drug Monitoring   Japanese Society of Pharmaceutical Health Care and Sciences   The Pharmaceutical Society of Japan   The Japanese Society for the study of Xenobiotics   

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 
    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 
    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 
    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 
    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 
    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 
    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
  • 重症病態後の患者におけるエドキサバン関連出血の予測モデルの構築
    三上 龍生, 早川 峰司, 今井 俊吾, 前川 邦彦, 山崎 浩二郎, 菅原 満, 武隈 洋
    日本血栓止血学会誌 33 2 269 - 269 (一社)日本血栓止血学会 2022年05月
  • 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 (一社)日本TDM学会 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 (一社)日本TDM学会 2022年05月
  • 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05月 
    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.
  • Yoh Takekuma, Shungo Imai, Mitsuru Sugawara
    YAKUGAKU ZASSHI 142 4 331 - 336 2022年04月01日
  • Soyoko Kaburaki, Eri Yoshimura, Yasushi Miyamoto, Shungo Imai, Hitoshi Kashiwagi, Hidefumi Ueno, Mitsuru Sugawara, Yoh Takekuma
    Geriatrics & Gerontology International 2022年03月30日
  • 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 47 7 1010 - 1019 2022年03月07日 
    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.
  • 大規模レセプトデータベースを用いたボリコナゾールの治療薬物モニタリング実施に関する実態調査
    宮井 貴之, 今井 俊吾, 百 賢二, 柏木 仁, 佐藤 夕紀, 菅原 満, 武隈 洋
    日本薬学会年会要旨集 142年会 27G - am09S (公社)日本薬学会 2022年03月
  • ビッグデータとデータマイニング手法を用いたリネゾリド誘発性血小板減少症の要因分析
    井上 優希, 武隈 洋, 宮井 貴之, 柏木 仁, 佐藤 夕紀, 菅原 満, 今井 俊吾
    日本薬学会年会要旨集 142年会 28H - pm13S (公社)日本薬学会 2022年03月
  • 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 
    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 7306 patients that were enrolled, VIN occurred in 14.2% of them (1035). 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.
  • 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 2022年02月 
    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.
  • 窪田 篤人, 寺崎 将, 小林 正紀, 室本 竜太, 青栁 亮一, 武隈 洋, 菅原 満, 小島 弘幸
    日本毒性学会学術年会 49.1 S39-5  日本毒性学会 2022年 
    はじめに 炎症性腸疾患(IBD)は、腸管の慢性炎症を呈する自己免疫疾患である。本邦における患者数は、近年増加の一途を辿り患者数は30万人を超えると推測されている。これまでの報告からIBDの病態形成には、遺伝的要因を基盤とした免疫機能、環境因子、腸内細菌叢など様々な因子が関与している。治療は内科的療法が主軸となり、抗炎症作用を有する 5-アミノサリチル酸(5-ASA)や免疫抑制剤などが用いられる。我々は、本邦における最大の疫学レセプトデータベースである JMDC Claims Database (累積母集団数1400万人)の2016年4月から2021年3月までの5年間に IBD と診断された全患者 44,328 名のデータを用い、治療傾向を調査した。その結果、頻度の高い治療として5-ASAや経口成分栄養(ED)療法が抽出された。 IBDと制御性T細胞 近年5-ASAは、既存の抗炎症機序の他に芳香族炭化水素受容体(AhR)を介して制御性T細胞(Treg)を誘導することが示唆された。更に、演者らは5-ASAがAhRの直接的なリガンドとなり、その結合部位について報告している(Kubota et al., Pharmacol. 2022)。そこで処方頻度の高いED療法についてもAhRに着目し、種々検討を行った。その結果、IBDモデルマウスに対するED療法は、腸管の炎症を抑制し、脾臓Tregの比率を有意に上昇させた。また、ED療法に含まれるトリプトファン(Trp)は、腸内細菌叢で代謝されAhRリガンドとなる事が知られていることから、Trpを強化したED療法をIBDモデルマウスに投与した。その結果、腸管の炎症抑制効果に加え、血中IL-10の上昇、TNF-αの抑制、脾臓Tregの上昇が認められた。本演題ではAhRに着目した免疫学的アプローチがIBDの病態制御の一助となることを紹介したい。
  • 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 
    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 
    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 
    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.
  • Yuki Sato, Yoh Takekuma, Takayuki Daisho, Hitoshi Kashiwagi, Shungo Imai, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 45 4 421 - 428 2022年 
    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.
  • Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
    Annals of Clinical Epidemiology 4 1 6 - 10 2022年
  • Kazuki Uchiyama, Yoshitaka Saito, Tatsuhiko Sakamoto, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Anticancer research 42 1 343 - 348 2022年01月 
    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
  • Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Mitsuru Sugawara
    Scientific reports 11 1 23298 - 23298 2021年12月02日 
    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.
  • 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 
    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, Takashi Takeshita, Mitsuru Sugawara
    Case Reports in Oncology 14 3 1277 - 1282 2021年09月09日 
    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/m2), 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 
    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)
  • 大規模レセプトデータベースを用いたボリコナゾールの治療薬物モニタリング実施に関する実態調査
    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 
    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)
  • 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 (一社)日本医薬品情報学会 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 (一社)日本臨床腫瘍薬学会 2021年05月
  • 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 
    【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 
    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)
  • 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)
  • 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 (公社)日本薬学会 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 (公社)日本薬学会 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 (公社)日本薬学会 2021年03月
  • Yoshitaka Saito, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
    Biological & pharmaceutical bulletin 44 12 1819 - 1823 2021年 
    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.
  • Aoyama, T., Kuriyama, H., Sato, Y., Imai, S., Kashiwagi, H., Sugawara, M., Takekuma, Y.
    Biol Pharm Bull 44 8 1101 - 1110 2021年 [査読有り]
     
    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.
  • Saito, Y., Uchiyama, K., Sakamoto, T., Yamazaki, K., Kubota, K., Takekuma, Y., Komatsu, Y., Sugawara, M.
    Yakugaku Zasshi 141 8 1023 - 1030 2021年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Takeuchi, S., Komatsu, Y., Sugawara, M.
    Int J Clin Pharmacol Ther 59 12 787 - 793 2021年 [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.
  • Tatsumi, M., Kumagai, S., Abe, T., Murakami, S., Takeda, H., Shichinohe, T., Watanabe, Y., Katayama, S., Hirai, S., Honda, A., Takekuma, Y., Sugawara, M.
    J Pharm Health Care Sci 7 1 16 - 16 2021年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Kobayashi, M., Sakamoto, T., Yamashita, H., Sugawara, M.
    Support Care Cancer 2021年 [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.
  • Saito, Yoshitaka, Takekuma, Yoh, Furuta, Megumi, Sugawara, Mitsuru
    Case Reports in Oncology 1418 - 1421 2021年 [査読有り]
     
    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.
  • Yamaguchi, A., Saito, Y., Okamoto, K., Narumi, K., Furugen, A., Takekuma, Y., Sugawara, M., Kobayashi, M.
    Support Care Cancer 2021年 [査読有り]
  • Tsutsumi, T., Imai, S., Kashiwagi, H., Sato, Y., Sugawara, M., Takekuma, Y.
    Eur J Clin Pharmacol 78 2 279 - 286 2021年 [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.
  • Yamashita, S., Imai, S., Momo, K., Kashiwagi, H., Sato, Y., Sugawara, M., Takekuma, Y.
    Biol Pharm Bull 44 8 1151 - 1155 2021年 [査読有り]
     
    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.
  • Imai, S., Nasuhara, Y., Momo, K., Oki, H., Kashiwagi, H., Sato, Y., Miyai, T., Sugawara, M., Takekuma, Y.
    Biol Pharm Bull 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.
  • Imai, S., Kashiwagi, H., Sato, Y., Miyai, T., Sugawara, M., Takekuma, Y.
    Br J Clin Pharmacol 88 3 1211 - 1222 2021年 [査読有り]
  • Watanabe, Y., Saito, Y., Mitamura, T., Takekuma, Y., Sugawara, M.
    J Pharm Health Care Sci 7 1 21 - 21 2021年 [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.
  • Uchiyama, K., Saito, Y., Takekuma, Y., Yuki, S., Sugawara, M.
    Case Rep Oncol 14 2 806 - 811 2021年 [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.
  • Sato, Y., Yamaguchi, K., Ogawa, M., Takekuma, Y., Sugawara, M.
    PLoS One 16 6 e0253066  2021年 [査読有り]
     
    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.
  • Kagami, K., Ishiguro, N., Yamada, T., Niinuma, Y., Iwasaki, S., Taki, K., Fukumoto, T., Hayasaka, K., Nishida, M., Sugita, J., Teshima, T., Sugawara, M., Takekuma, Y.
    Am J Infect Control 2021年 [査読有り]
  • Imai, S., Momo, K., Kashiwagi, H., Sato, Y., Miyai, T., Sugawara, M., Takekuma, Y.
    Expert Opin Drug Saf 20 10 1257 - 1266 2021年 [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.
  • Saito, Y., Uchiyama, K., Sakamoto, T., Kubota, K., Oki, H., Iwai, M., Takekuma, Y., Komatsu, Y., Sugawara, M.
    Biol Pharm Bull 44 3 293 - 297 2021年 [査読有り]
     
    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.
  • Saito, Y., Tamaki, S., Hasegawa, H., Takahashi, K., Tokutome, A., Takekuma, Y., Yamashita, H., Komatsu, Y., Sugawara, M.
    Biol Pharm Bull 44 4 474 - 477 2021年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Yuki, S., Komatsu, Y., Sugawara, M.
    Case Rep Oncol 14 1 207 - 211 2021年 [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.
  • Nashimoto, S., Yagi, S., Takeda, N., Nonaka, M., Takekuma, Y., Sugawara, M., Sato, Y.
    Biochim Biophys Acta Biomembr 1863 2 183508 - 183508 2021年 [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.
  • Nishimura, A., Furugen, A., Umazume, T., Kitamura, S., Soma, M., Noshiro, K., Takekuma, Y., Sugawara, M., Iseki, K., Kobayashi, M.
    Breastfeed Med 16 5 2021年 [査読有り]
  • Kumai, M., Imai, S., Kato, S., Koyanagi, R., Tsuruga, K., Yamada, T., Takekuma, Y., Sugawara, M.
    Biol Pharm Bull 44 4 593 - 598 2021年 [査読有り]
     
    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.
  • Kagami, K., Ishiguro, N., Yamada, T., Niinuma, Y., Iwasaki, S., Taki, K., Fukumoto, T., Hayasaka, K., Oyamada, R., Watanabe, T., Nishida, M., Sugita, J., Teshima, T., Sugawara, M., Takekuma, Y.
    J Infect Chemother 27 3 473 - 479 2021年 [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.
  • Imai, S., Momo, K., Kashiwagi, H., Miyai, T., Sugawara, M., Takekuma, Y.
    Biol Pharm Bull 44 3 448 - 452 2021年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Kobayashi, M., Shinagawa, N., Shimizu, Y., Kinoshita, I., Dosaka-Akita, H., Iseki, K., Sugawara, M.
    Eur J Clin Pharmacol 77 3 381 - 388 2021年 [査読有り]
     
    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.
  • 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 
    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)
  • 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 
    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)
  • 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]
     
    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]
     
    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)
  • 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 (公社)日本化学療法学会 2020年09月
  • Uchiyama, K., Saito, Y., Takekuma, Y., Sugita, J., Teshima, T., Sugawara, M.
    J Oncol Pharm Pract 1078155220980815 - 1078155220980815 2020年 [査読有り]
     
    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.
  • Saito, Y., Uchiyama, K., Sakamoto, T., Yamazaki, K., Kubota, K., Takekuma, Y., Komatsu, Y., Sugawara, M.
    Biol Pharm Bull 43 12 1969 - 1974 2020年 [査読有り]
  • Miyai, T., Imai, S., Kashiwagi, H., Sato, Y., Kadomura, S., Yoshida, K., Yoshimura, E., Teraya, T., Tsujimoto, T., Kawamoto, Y., Itoh, T., Ueno, H., Goto, Y., Takekuma, Y., Sugawara, M.
    Antibiotics (Basel) 9 12 920 - 920 2020年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Komatsu, Y., Sugawara, M.
    J Oncol Pharm Pract 27 4 1078155220956691 - 1078155220956691 2020年 [査読有り]
     
    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.
  • Imai, S., Momo, K., Kashiwagi, H., Miyai, T., Sugawara, M., Takekuma, Y.
    Biol Pharm Bull 43 10 1519 - 1525 2020年 [査読有り]
     
    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.
  • Nashimoto, S., Takekawa, Y., Takekuma, Y., Sugawara, M., Sato, Y.
    Drug Metab Pharmacokinet 35 6 527 - 533 2020年 [査読有り]
     
    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.
  • Saito, Y., Takekuma, Y., Kobayashi, M., Komatsu, Y., Sugawara, M.
    Support Care Cancer 29 6 3277 - 3285 2020年 [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.
  • Imai, S., Momo, K., Kashiwagi, H., Miyai, T., Sugawara, M., Takekuma, Y.
    J Pharm Health Care Sci 6 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.
  • Imai, S., Kadomura, S., Momo, K., Kashiwagi, H., Sato, Y., Miyai, T., Sugawara, M., Takekuma, Y.
    J Infect Chemother 26 11 1224 - 1228 2020年 [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.
  • Imai, S., Momo, K., Kashiwagi, H., Miyai, T., Sugawara, M., Takekuma, Y.
    Int J Clin Pharm 42 5 1369 - 1373 2020年 [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.
  • Sato, Y., Joumura, T., Takekuma, Y., Sugawara, M.
    Eur J Pharm Biopharm 154 210 - 213 2020年 [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.
  • Imai, S., Takekuma, Y., Kashiwagi, H., Miyai, T., Kobayashi, M., Iseki, K., Sugawara, M.
    PLoS One 15 7 e0236789 - 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.
  • Kumai, M., Maeda, Y., Miura, M., Tsuruga, K., Yamada, T., Takekuma, Y., Sugawara, M.
    Case Rep Oncol 13 1 281 - 284 2020年 [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.
  • Kadomura, Shota, Takekuma, Yoh, Imai, Shungo, Kashiwagi, Hitoshi, Kawamoto, Kotaro, Itoh, Tatsuya, Sugawara, Mitsuru
    BPB Reports 3 2 65 - 69 2020年 [査読有り][通常論文]
  • Imai, S., Momo, K., Kashiwagi, H., Miyai, T., Sugawara, M., Takekuma, Y.
    Pharmacoepidemiol Drug Saf 29 8 873 - 880 2020年 [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.
  • Tanaka, H., Hiraga, H., Takekuma, Y., Harabayashi, T., Nagamori, S., Endo, M., Sugawara, M.
    Biol Pharm Bull 43 5 762 - 766 2020年 [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.
  • Imai, Shungo, Takekuma, Yoh, Miyai, Takayuki, Sugawara, Mitsuru
    Biological and 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.
  • Sasaki, M., Aoyama, T., Sugawara, M., Takekuma, Y.
    Drug Metab Pharmacokinet 35 1 102 - 110 2020年 [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.
  • Sato, Yuki, Sato, Yuki, Yokoyama, Sayaka, Yokoyama, Sayaka, Yamaki, Yoshiaki, Yamaki, Yoshiaki, Nishimura, Yuta, Nishimura, Yuta, Miyashita, Mami, Miyashita, Mami, Maruyama, Shingo, Maruyama, Shingo, Takekuma, Yoh, Takekuma, Yoh, Sugawara, Mitsuru, Sugawara, Mitsuru
    European Journal of Pharmaceutical Sciences 142 105144 - 105144 2020年 [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.
  • Sakamoto, T., Saito, Y., Kobayashi, M., Yamada, T., Takekuma, Y., Nakai, M., Ogawa, K., Iseki, K., Sugawara, M.
    Support Care Cancer 28 7 3251 - 3257 2020年 [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.
  • 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.
  • 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] (公社)日本薬剤師会 2017年10月
  • 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 alpha-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 alpha-tocopherol is also inhibited by ezetimibe. This study investigated the influence of ezetimibe on the absorption of alpha-tocopherol with single administration and long-term administration. An approach to avoid its undesirable consequence was also examined. alpha-Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of alpha-tocopherol and tissue concentrations were investigated. The plasma concentration of alpha-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 alpha-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 alpha-tocopherol and ezetimibe. The absorption of alpha-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 alpha-tocopherol. Copyright (C) 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)
  • 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]
  • Yuto Takekawa, Yuki Sato, Yoshiaki Yamaki, Mei Imai, Kazuma Noto, Masato Sumi, Yoh Takekuma, Ken Iseki, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 39 3 301 - 307 2016年03月 [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 Cl-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 mu m) 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.
  • 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.
  • Yuki Tazawa, Ippei Usukubo, Kazuki Takada, Yoh Takekuma, Yoshihiro Shibayama, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 37 8 1323 - 1329 2014年08月 [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.
  • 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 Sato, Hanami Mutoh, Mika Suzuki, Yoh Takekuma, Ken Iseki, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 36 12 2012 - 2017 2013年12月 [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 AND PHARMACEUTICAL SCIENCES 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 4 degrees C was about 40% less that that at 37 degrees C.
  • Yuki Tazawa, Kazunori Matsumura, Yoh Takekuma, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 35 7 1132 - 1136 2012年07月 [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 mu g/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 mu g/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 mu g/mL) of VP-16. It was confirmed that these concentrations did not influence cell viability. Viability of subsequently exposed to 1-20 mu g/mL was not different from that of control cells not treated with VP-16. VP-16 caused cell cycle arrest at G(2)/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.
  • 高橋夏子, 小林正紀, 板垣史郎, 平野剛, 武隈洋, 菅原満, 井関健, 井関健
    薬学雑誌 132 6 777 - 783 2012年06月 [査読有り][通常論文]
     
    The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs (cisplatin, carboplatin, paclitaxel and gemcitabine) was performed by the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The four anticancer drugs were grouped by IC50 values (inhibitory concentration, 50%) in a time-dependent manner and a concentration-dependent manner. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.
  • Yoh Takekuma, Keiji Yagisawa, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 35 2 151 - 163 2012年02月 [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.
  • Miki Komatsu, Masahiko Takahata, Mitsuru Sugawara, Yoh Takekuma, Takashi Kato, Manabu Ito, Yuichiro Abe, Tohru Irie, Norimasa Iwasaki, Akio Minami
    EUROPEAN SPINE JOURNAL 19 12 2149 - 2155 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.
  • 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)
  • Hitoshi Kashiwagi, Kojiro Yamazaki, Yoh Takekuma, Vadivel Ganapathy, Mitsuru Sugawara
    AMINO ACIDS 36 2 219 - 230 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 V (max), not K (m). 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.
  • 三浦正義, 阿知波一人, 下田直彦, 武隈 洋, 原田 浩
    今日の移植 22 6 718 - 722 (株)日本医学館 2009年 [査読無し][通常論文]
     
    2歳女児。生下時より下肢浮腫を認め、先天性ネフローゼ症候群の診断となった。生後7ヵ月で左腎摘、腹膜透析カテーテル留置、胃瘻造設を施行した。生後12ヵ月で腹膜透析を導入した。母親をドナーとして生体腎移植(一次移植)を実施した。移植術の翌日に腎静脈・下大静脈血栓症を発症し、緊急手術にて移植腎を摘出した。一次移植の2ヵ月後に、叔母をドナーとして二次移植を予定したが、クロスマッチが陽性化したため、血漿交換、リツキシマブ投与による減感作療法後に移植を行った。二次移植後は移植腎機能が速やかに発現した。免疫抑制の維持に困難をきわめ、急性拒絶反応を発症し、その治療後にEBウイルス血症をきたし管理に難渋した。
  • 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]
  • 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。
  • 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 一般社団法人 日本医療薬学会 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 一般社団法人 日本医療薬学会 2008年
  • Yoh Takekuma, Toru Takenaka, Koujiro Yamazaki, Kazuyuki Ueno, Mitsuru Sugawara
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 30 11 2146 - 2153 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 stereo selective 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 - 542 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 fie 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 [査読有り][通常論文]
     
    We investigated the mechanism of the transport of ribavirin (1--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 AM) 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 values were 18.0 mu M, 14.2 mu M, 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. (c) 2006 Elsevier B.V. All rights reserved.
  • Yoh Takekuma, Haruka Kakiuchi, Koujiro Yamazaki, Seiji Miyauchi, Takashi Kikukawa, Naoki Kamo, Vadivel Ganapathy, Mitsuru Sugawara
    JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES 10 1 71 - 85 2007年01月 [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 mu M and 41.5 +\- 11.5 mu M, 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 mu M and 1036.8 +/- 330.5 mu M, 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.
  • 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 一般社団法人 日本医療薬学会 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 一般社団法人 日本医療薬学会 2007年
  • 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)
  • 渡井至彦, 森田研, 三浦正義, 福澤信之, 小野武紀, 柴田武, 野々村克也, 帯金克行, 中嶋泰志, 佐々木聡, 松浦麻耶, 山崎浩二郎, 武隈洋
    日本小児腎不全学会雑誌 26 242 - 244 2006年 [査読無し][通常論文]
  • Y Takekuma, T Takenaka, M Kiyokawa, K Yamazaki, H Okamoto, A Kitabatake, H Tsutsui, M Sugawara
    JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES 9 1 101 - 112 2006年01月 [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.
  • M Sugawara, S Kadomura, He, X, Y Takekuma, N Kohri, K Miyazaki
    EUROPEAN JOURNAL OF 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. (c) 2005 Elsevier B.V. All rights reserved.
  • Sugawara M, Mochizuki T, Takekuma Y, Miyazaki K
    Biochimica et biophysica acta 1714 2 85 - 92 2 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, 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
  • He, X, M Sugawara, Y Takekuma, K Miyazaki
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 48 7 2604 - 2609 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.
  • S Kishino, M Ogawa, Y Takekuma, M Sugawara, T Shimamura, H Furukawa, S Todo, K Miyazaki
    CLINICAL TRANSPLANTATION 18 2 124 - 129 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.
  • 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
  • He, X, S Kadomura, Y Takekuma, M Sugawara, K Miyazaki
    JOURNAL OF PHARMACEUTICAL SCIENCES 93 1 71 - 77 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(R) tablets) and glibenclamide preparation (Euglucon(R) 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. (C) 2004 Wiley-Liss, Inc.
  • 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.
  • He, X, M Sugawara, M Kobayashi, Y Takekuma, K Miyazaki
    INTERNATIONAL JOURNAL OF PHARMACEUTICS 263 1-2 35 - 44 2003年09月 [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 oil 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 ill 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/mm. 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 oil 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. (C) 2003 Elsevier B.V. All rights reserved.
  • 武隈 洋, 山下 恭範, 岩井 美和子, 志賀 弘康, 須田 範行, 岸野 吏志, 宮崎 勝巳
    医療薬学 29 2 225 - 229 日本医療薬学会 2003年04月 [査読有り][通常論文]
     
    Cardioplegic solution (CPS), a pharmaceutical product manufactured at our hospital, is used for operative myocardial protection. Glucose, one of the elements of CPS, is known to disintegrate into formic acid, levulinic acid and 5-Hydroxymethylfurfural (5-HMF). Accordingly, the stability and their shelf life of CPS were evaluated by pH variation, visual inspection and the amount of 5-HMF. CPS was preserved for 12 months at room temperature (25℃) and at 4℃(under room light or in darkness) after autoclaving at 115℃ and 0.7 kg/cm^2 for 30 min. The pH of the sample was observed along with a peri...
  • 武隈洋, 志賀弘康, 山下恭範, 須田範行, 岩井美和子, 岸野吏志, 宮崎勝巳
    医療薬学 29 1 62 - 65 日本医療薬学会 2003年02月 [査読有り][通常論文]
     
    A 0.625% povidone-iodine solution (PVP-I) for eye washing, a pharmaceutical product prepared in our hospital, is used to disinfect the conjunctival sac in eye surgery. Since iodine is unstable, its bactericidal activity is reduced when PVP-I is diluted. Therefore, the stability of a 0.625% PVP-I solution under various preservation conditions was studied. Its stability was evaluated by pH variation, visual inspection and the residual rate of available iodine. The 0.625% PVP-I solution was stored for 5 weeks at room temperature (25℃) and at 4℃ under diffused light or in a dark place. The amount of available iodine was determined by the oxidation-reduction titration method according to the fourteenth revised edition of the Japanese Pharmacopoeia (JPXIV). No apparent changes were found by pH variation or visual inspection after storage for 5 weeks either at 4℃ or 25℃. The residual rates of available iodine after 5 weeks of storage were 91% at 25℃ and 98% at 4℃, thus suggesting that a reduction in available iodine is smaller at 4℃ than at 25℃. This finding also suggests that a reduction in available iodine is dependent on temperature. The results of this study indicate that a 0.625% PVP-I solution for eye washing remains stable for 5 weeks if stored at a temperature of less than 4℃.
  • Mitsuru Sugawara, Masaya Kato, Mayumi Kitakubo, Yoh Takekuma, Vadivel Ganapathy, Katsumi Miyazaki
    Drug Metabolism And Pharmacokinetics 18 3 186 - 193 2003年02月01日 [査読有り][通常論文]
     
    Summary: 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 B°, 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 B°) 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. © 2003, The Japanese Society for the Study of Xenobiotics. All rights reserved.
  • S Kishino, A Nomura, S Itoh, T Nakagawa, Y Takekuma, M Sugawara, H Furukawa, S Todo, K Miyazaki
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 58 9 621 - 628 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.
  • S Kishino, Y Takekuma, M Sugawara, T Shimamura, H Furukawa, S Todo, K Miyazaki
    JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 780 2 289 - 294 2002年11月 [査読有り][通常論文]
     
    We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovirand/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 mug/ml plasma) or acyclovir (0.1-20 mug/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 mug h/ml and 7.16 mug 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. (C) 2002 Elsevier Science B.V. All rights reserved.
  • M Hiratsuka, Y Takekuma, N Endo, K Narahara, SI Hamdy, Y Kishikawa, M Matsuura, Y Agatsuma, T Inoue, M Mizugaki
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 58 6 417 - 421 2002年09月 [査読有り][通常論文]
     
    Objective: The goal of this study was to determine the frequencies of allelic variants of CYP2B6 and CYP3A5 in the Japanese population. Methods: Genotyping of CYP2B6 (*2, *3, *4, *5, *6, and *7)and CYP3A5 (*2, *3, *4, *5, and *6) was carried out in 265 unrelated Japanese subjects by polymerase chain reaction (PCR), restriction fragment length polymorphism and allele-specific, real-time PCR assays. Results: Allele frequencies for CYP2B6*2, *3, *4, *5, *6, and *7 in 256 Japanese subjects were 0.047, 0, 0.093, 0.011, 0.164, and 0, respectively. Ethnic variation in allele frequencies relative to that in Caucasian subjects was observed for CYP2B6*4 (0.093 vs 0.040), *5 (0.011 vs 0.109), *6 (0.164 vs 0.256), and *7 (0 vs 0.030). Allele frequencies for CYP3A5*2, *3, *4, *5, and *6 in 265 Japanese subjects were 0, 0.740, 0, 0.004, and 0, respectively. The frequency of the CYP3A5*1 allele is 2.8 times higher in Japanese than in Caucasians. Conclusions: Our results contribute to a better understanding of the molecular basis of ethnic differences in drug response, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs that are substrates for CYP2B6 and CYP3A5 in the Japanese population.
  • 越浪由加, 細井健, 武隈洋, 小林道也, 森本裕二, 丸藤哲, 古川裕之, 藤堂省, 宮崎勝巳
    TDM研究 19 1 39 - 43 2002年01月 [査読有り][通常論文]
  • Masahiro Hiratsuka, Yoh Takekuma, Masaki Matsuura, Kaori Narahara, Tomoko Inoue, Samar Hamdy Ismail, Naomi Endo
    Drug Metabolism and Pharmacokinetics 17 4 357 - 362 2002年 [査読有り][通常論文]
     
    To investigate the association between NAT2 genotypes and the incidence of isoniazid (INH)-induced adverse reactions, in the hope of identifying a pharmacogenetic approach that could be useful in the prediction and prevention of adverse reactions in Japanese patients, we retrospectively studied the genotypes of NAT2 in 102 Japanese patients treated with INH (without rifampicin co-administration). The subjects were classiôed into three groups according to their genotypes: rapid-type, intermediate-type, and slow-type. The clinical conditions of the patients were followed-up in order to evaluate the development of any adverse drug reactions (ADRs) and correlate them with patient genotypes. Six out of the 102 patients (5.9z) developed various ADRs following INH treatment. These reactions included nauseaWvomiting, fever, visual impairment, and peripheral neuritis. We found a statistically signi ôcant diference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was signi ôcantly higher in the slow type than in the other two types, as 5 out of the 6 ADR patients were of the slow-type, and the other one was of the intermediate-type, while no patients of the rapid-type developed any ADRs. The results indicated that the genes coding for slow acetylation were associated with the incidence of serious ADRs following INH treatment. Our ôndings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH. © 2002, The Japanese Society for the Study of Xenobiotics. All rights reserved.
  • Kishino Satoshi, Koshinami Yuka, Komai Tomomi, Suda Noriyuki, Takekuma Yoh, Takeuchi Ichiro, Koyanagi Tomohiko, Miyazaki Katsumi
    TDM研究 18 4 349 - 354 2001年10月 [査読有り][通常論文]
  • S Kishino, Y Koshinami, T Hosoi, N Suda, Y Takekuma, S Gandoh, H Furukawa, S Todo, K Miyazaki
    THERAPEUTIC DRUG MONITORING 23 1 4 - 8 2001年02月 [査読有り][通常論文]
     
    Fungal infections are still one of the main causes of death and complications after solid organ and bone marrow transplants. The authors evaluated the effect of continuous hemodiafiltration (CHDF) on the pharmacokinetics of fluconazole in liver transplant recipients. Six liver transplant patients (primary biliary cirrhosis, n = 2; fulminant hepatitis, n = 2: viral hepatitis, n = 2) were enrolled in this study. In one patient not receiving CHDF, the fluconazole levels increased with increasing dosages. in contrast, in patients undergoing CHDF, the dosage of fluconazole was increased from 100 mg/d to 200 mg/d, but fluconazole did not reach the targeted levels. It appears that the targeted trough level cannot be achieved by administration of fluconazole at a dosage of 100 to 200 mg/d during CHDF. A higher dosage (600-1000 mg/d) of fluconazole may be required to achieve the therapeutic drug level in patients undergoing CHDF. In patients undergoing CHDF, fluconazole was given at a dosage of 800 mg/d and reached the targeted levels. In addition, after CHDF, the dosage of fluconazole was decreased to 100 mg/d, and fluconazole reached the near-targeted trough level. These results demonstrate that CHDF removes fluconazole from the blood at an Efficiently high rate, resulting in its ineffective blood level. To guarantee safe and effective fluconazole therapy, the trough levels should be monitored routinely during CHDF.
  • 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.
  • 沖洋充, 武隈洋, 中島かおり, 駿河幸恵, 清川真美, 榊原則寛, 蔵田俊一, 小林道也, 宮崎勝巳
    病院薬学 24 3 317 - 327 日本病院薬剤師会 1998年06月 [査読有り][通常論文]
     
    A computer system for delivering drug information leaflets for patients has been introduced at Hokkaido University Hospital. This system can print out the trade name, color picture, dosage and administration, efficacies, symptoms of side effects, and directions at the time of taking medicine can store about 1,400 items. The information regarding the efficacies and symptoms of side effects was carefully reviewed beforehand by medical doctors. These information leaflets are now provided to out-patients under instructions from medical doctors. Evidence thus far suggests that these leaflets produce a favorable impression on patients for a safety and a proper use of medicines.
  • 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 The Japanese Society for the Study of Xenobiotics 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.
  • 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

書籍

  • 武隈洋 (担当:分担執筆範囲:7章EBMと臨床研究 B臨床研究の手法)
    南江堂 2018年12月 (ISBN: 9784524403592) ix, 245p
  • 日本TDM学会TDM実例集編集委員会, 日本TDM学会 (担当:分担執筆範囲:46 血液透析施行中の高度腎機能障害患者に対するリネゾリドの投与量設計)
    じほう 2016年05月 (ISBN: 9784840748476) 215p
  • コンパス 医薬品情報学-理論と演習-
    武隈 洋 (担当:分担執筆範囲:7章EBMと臨床研究, B臨床研究の手法)
    南江堂 2015年09月
  • Applied 臨床薬物動態学
    武隈 洋 (担当:分担執筆範囲:2・6 免疫抑制薬,2・11・1 オピオイド鎮痛薬)
    京都廣川書店 2013年06月
  • 事前実習テキスト アルティメイト
    武隈 洋 (担当:分担執筆範囲:第2章 処方せんと調剤)
    京都廣川書店 2010年04月

講演・口頭発表等

  • デキサメタゾン予防投与下におけるタキサン 起因性疼痛症候群のリスク因子に関する検討  [通常講演]
    坂本達彦, 齋藤佳敬, 武隈 洋, 小林正紀, 山下啓子, 菅原 満
    第31回日本医療薬学会年会要旨集 2021年10月
  • シスプラチン誘発性消化器症状に対する制酸薬の有効性評価
    谷口理, 齋藤佳敬, 武隈洋, 品川尚文, 木下一郎, 秋田弘俊, 菅原満
    第31回日本医療薬学会年会要旨集 2021年10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 2021年05月 (一社)日本臨床腫瘍薬学会
  • 武隈 洋
    TDM研究 2021年05月 (一社)日本TDM学会
  • JMDCレセプトデータベースを用いた臨床研究  [通常講演]
    武隈 洋, 今井俊吾, 菅原 満
    日本薬学会第141年会 2021年03月 シンポジウム・ワークショップパネル(公募)
  • 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 2021年03月 (公社)日本薬学会
  • 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 2021年03月 (公社)日本薬学会
  • 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 2021年03月 (公社)日本薬学会
  • 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 2020年11月 日本腎臓病薬物療法学会
  • 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 2020年09月 (公社)日本化学療法学会
  • 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 2020年03月 (公社)日本薬学会
  • 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 2020年03月 (公社)日本薬学会
  • 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 2020年03月 (公社)日本薬学会
  • 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 2020年03月 (公社)日本薬学会
  • 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 2020年03月 (公社)日本薬学会
  • Improvement of renal function estimation equations for elderly Japanese people  [招待講演]
    武隈 洋
    The 5th Japan-Taiwan Joint Symposium for Pharmaceutical Sciences 2019年08月 口頭発表(招待・特別)
  • 心不全患者のカルベジロール血中モニタリングと光学異性体間相互作用  [通常講演]
    武隈 洋
    2019年07月 シンポジウム・ワークショップパネル(指名)
  • バンコマイシンの初回投与設計ノモグラム(抗菌薬TDMガイドライン2016)の臨床的検証  [通常講演]
    田中 寛之, 森岡 悠紀, 武隈 洋, 藤田 崇宏, 遠藤 雅之, 菅原 満
    第36回日本TDM学会・学術大会 2019年05月 口頭発表(一般)
  • 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  [通常講演]
    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139年会 2019年03月 口頭発表(一般)
  • Xenopus laevis oocytesを用いたNiemann-Pick C1-Like 1(NPC1L1)発現系の最適化  [通常講演]
    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139年会 2019年03月 口頭発表(一般)
  • エンテロイドを用いた薬物排出トランスポーターの機能解析  [通常講演]
    小関 千尋, 石川 岳彦, 佐藤 夕紀, 武隈 洋, 菅原 満
    日本薬学会139年会 2019年03月 口頭発表(一般)
  • 門脈およびリンパ管への薬物移行を考慮した消化管吸収の評価  [通常講演]
    定村 樹, 佐藤 夕紀, 武隈 洋, 菅原 満
    日本薬学会139年会 2019年03月 口頭発表(一般)
  • 加齢による薬物動態の変化について  [招待講演]
    武隈 洋
    第9回 札幌薬剤師会 臨床薬学講演会 2018年09月 公開講演,セミナー,チュートリアル,講習,講義等
  • 消化管活動性がニロチニブの吸収性に及ぼす影響  [通常講演]
    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2018 2018年06月 ポスター発表
  • 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  [通常講演]
    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
    日本薬剤学会第33年会 2018年05月 口頭発表(一般)
  • 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  [通常講演]
    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
    日本薬学会第138年会 2018年03月 口頭発表(一般)
  • 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  [通常講演]
    伊藤 圭祐, 佐々木萌子, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第138年会 2018年03月 口頭発表(一般)
  • 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  [通常講演]
    蕪木素代子, 吉村恵理, 小嶋希望, 上野博文, 菅原 満, 武隈 洋
    日本薬学会第138年会 2018年03月 ポスター発表
  • シクロプロパンの構造特性に基づく膜透過性環状ペプチドの設計と合成  [通常講演]
    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 2018年03月 口頭発表(一般)
  • Emulsification using oxa acids for oral administration and the improvement of intestinal absorption of Coenzyme Q10  [通常講演]
    Yuki Sato, Sayaka Yokoyama, Yoshiaki Yamaki, Mami Miyashita, Yoh Takekuma, Shingo Maruyama, Mitsuru Sugawara
    8th Joint Meeting of Society for Free Radical Research Australasia and Japan with International Symposium on Coenzyme Q10 2017年12月 ポスター発表
  • パゾパニブの投与量と投与継続期間の後ろ向き調査  [通常講演]
    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
    第27回日本医療薬学会年会 2017年11月 口頭発表(一般)
  • 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  [通常講演]
    濱野宏美, 土井正剛, 武隈 洋, 菅原 満, 一木崇宏
    第50回日本薬剤師会学術大会 2017年10月 ポスター発表
  • Continuous cytostatic effects of BCR-ABL tyrosine kinase inhibitors (TKIs) after washout in human leukemic K562 cells  [通常講演]
    Tsuyoshi Aoyama, Yoh Takekuma, Masato Sumi, Yuki Sato, Mitsuru Sugawara
    15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT) 2017年09月 ポスター発表
  • パゾパニブの血中濃度に影響する因子の検討  [通常講演]
    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
    第32回日本TDM学会・学術大会 2017年09月 ポスター発表
  • パゾパニブの血中濃度に影響する因子の探索  [通常講演]
    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 2017年09月
  • テアニン錠剤(速放錠・徐放錠)の溶出性および吸収性の変動要因  [通常講演]
    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
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • 卵黄レシチンを用いた自己乳化製剤によるクルクミンの消化管吸収改善  [通常講演]
    宮下 真美, 横山 さや香, 佐藤 夕紀, 武隈 洋, 吉田 英人, 菅原 満
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • オキサ酸を乳化剤として用いたCoenzyme Q10の乳剤化と消化管吸収改善  [通常講演]
    横山 さや香, 宮下 真美, 佐藤 夕紀, 武隈 洋, 丸山 真吾, 菅原 満
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • 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グルクロン酸抱合反応に及ぼす光学異性体相互作用の評価  [通常講演]
    佐々木 萌子, 武隈 洋, 佐藤 夕紀, 鷲見 正人, 菅原 満
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • 慢性骨髄性白血病治療薬ダサチニブの消化管吸収に及ぼす消化管内pHおよびトランスポーターの影響  [通常講演]
    助畑 歩, 武隈 洋, 鷲見 正人, 佐藤 夕紀, 菅原 満
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • シクロプロパンの構造特性に基づく環状ペプチド膜透過性の飛躍的向上  [通常講演]
    植村 真衣, 松井 耕平, 桑原 智希, 渡邉 瑞貴, 福田 隼, 加藤 七海, 武隈 洋, 菅原 満, 周東 智
    日本薬学会第137年会 2017年03月 口頭発表(一般)
  • シクロプロパンの構造特性に基づく環状ペプチド膜透過性の飛躍的向上  [通常講演]
    植村 真衣, 松井 耕平, 桑原 智希, 渡邉 瑞貴, 福田 隼, 加藤 七海, 武隈 洋, 菅原 満, 周東 智
    日本薬学会年会要旨集 2017年03月
  • クロスポビドンを含む錠剤の 製剤処方による溶出性の違い  [通常講演]
    武隈 洋, 石坂 悠, 佐藤夕紀, 鷲見正人, 菅原 満
    第26回日本医療薬学会年会 2016年09月 口頭発表(一般)
  • パゾパニブの投与量と推定血中トラフ濃度の関連性の評価  [通常講演]
    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
    第49回 日本整形外科学会骨・軟部腫瘍学術集会 2016年07月 口頭発表(一般)
  • イマチニブの TDM により副作用軽減と治療継続が可能となった二重癌の一症例  [通常講演]
    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
    第33回日本TDM学会・学術大会 2016年05月 口頭発表(一般)
  • 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  [通常講演]
    佐藤夕紀, 八巻義朗, 竹川悠人, 武隈洋, 菅原満
    日本薬剤学会第31年会 2016年05月 口頭発表(一般)
  • 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  [通常講演]
    梨本俊亮, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満
    日本薬学会第136年会 2016年03月 口頭発表(一般)
  • 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16回日本医薬品情報学会総会・学術大会 2015年06月 口頭発表(一般)
  • 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, 野田敏宏, 平野卓哉, 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 ポスター発表
  • 骨肉腫MAP療法における2-compartment modelによる非タンパク結合Platinum推定CmaxとCDDP腎毒性の予測  [通常講演]
    田中寛之, 森岡悠紀, 深井雄太, 武隈 洋, 川口啓之, 平賀博明, 菅原満, 遠藤雅之
    第32回日本TDM学会・学術大会(松本) 2015年05月 ポスター発表
  • 高度腎機能障害および透析時のリネゾリド投与量設計  [招待講演]
    武隈 洋
    第32回日本TDM学会・学術大会(松本) 2015年05月 公開講演,セミナー,チュートリアル,講習,講義等
  • 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 口頭発表(一般)
  • 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  [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 口頭発表(一般)
  • 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 2015年03月 口頭発表(一般)
  • 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26回日本医療薬学会年会(名古屋) 2014年09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, 高崎雅彦
    第31回日本TDM学会学術大会(東京) 2014年05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
  • 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  [通常講演]
    武隈 洋, 高地里佳, 野田敏宏, 平野卓哉, 菅原 満
    第16回日本医薬品情報学会総会・学術大会(名古屋) 2013年08月
  • Intracellular uptake mechanism of lutein in retinal pigment epithelial cells  [通常講演]
    Yuki Sato, Yu Kondo, Masato Sumi, Yoh Takekuma, Mitsuru Sugawara
    5th World Conference on Drug Absorption, Transport and Delivery (WCDATD: Responding to Challenging Situations (BioMedical Centre (BMC),Uppsala, Sweden) 2013年06月 ポスター発表
  • 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  [通常講演]
    佐藤夕紀, 近藤 有, 武隈洋, 菅原満
    日本薬剤学会年会第28年会(名古屋) 2013年05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
  • 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
  • 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
  • IMPROVEMENT OF INTESTINAL ABSORPTION OF FUNCTIONAL FOODS, LUTEIN AND COENZYME Q10  [通常講演]
    Y. Sato, H. Mutoh, Y. Takekuma, K. Iseki, M. Sugawara
    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35回日本造血細胞移植学会総会(大阪) 2012年02月
  • 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  [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
    第19回医療薬学フォーラム(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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 抗MRSA薬リネゾリドとバンコマイシンの脊椎組織への移行性の違い  [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
  • 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腎移植患者の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
  • 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( American Association of Pharmaceutical Scientists ) Annual Meeting and Exposition(Atlanta, GA) 2008年11月 ポスター発表
  • 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
  • 感染性脊椎炎をターゲットとした新規抗MRSA薬リネゾリドの脊椎周辺組織への移行性に関する実験的研究  [通常講演]
    小松幹, 高畑雅彦, 武隈洋, 菅原満, 加藤貴志, 入江徹, 安倍雄一郎, 伊東学, 三浪明男
    第23回日本整形外科学会基礎学術集会(京都) 2008年10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
  • 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
  • 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
    第25会日本TDM学会学術大会(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
  • 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
  • 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
  • 全身性エリテマトーデス(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(群馬) 2007年
  • 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(群馬) 2007年
  • 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
  • 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
  • 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(multidrugresistance-associatedprotein2)及びOAT(organicanion 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
  • 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, 野々村克哉, 井関 健
    第40回日本臨床腎移植学会(石川) 2007年
  • Cooperation of concentrative nucleoside transporter (CNT) and equilibrative nucleoside transporter (ENT) in the uptake of ribavirin  [通常講演]
    Takashi Yamamoto, Yoh Takekuma, Takeshi Hirano, Ken Iseki, Seiji Miyauchi, Takashi Kikukawa, Naoki Kamo, Mitsuru Sugawara
    第21回日本薬物動態学会年会(東京) 2006年
  • 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
  • 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
  • 高度腎機能障害患者におけるリネゾリドの体内動態変動  [通常講演]
    山﨑浩二郎, 宮本剛典, 菅原 満, 武隈 洋, 太田薫子, 伊藤洋子, 南須原康行, 西村正治, 井関 健
    第14回クリニカルファーマシーシンポジウム(大阪) 2006年
  • 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
  • 腎移植患者におけるタクロリムス併用時の小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
    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変動に及ぼすグルクロン酸転移酵素および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 顕, 筒井裕之, 宮崎勝巳
    第22回日本TDM学会学術大会(沖縄) 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
  • 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
  • LIMITED SAMPLING STRATEGY FOR THERAPEUTIC DRUG MONITORING OF MYCOPHENOLIC ACID AFTER RENAL TRANSPLANTATION  [通常講演]
    Yoshihiko Watarai, Ken Morita, Nobuyuki Fukuzawa, Katsuya Nonomura, Yo Takekuma, Kojiro Yamazaki, Harumi Takada, Katsumi Miyazaki
    The 3rd international congress on immunosuppression(San Diego, USA) 2004年12月
  • Regulatorymechanisms 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]
    Hitoshi Kashiwagi, Mitsuru Sugawara, Yoh Takekuma, Vadivel Ganapathy, Katsumi Miyazaki
    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]
    Masaya Oda, Takahiro Mochizuki, Yoh Takekuma, Mitsuru Sugawara, Katsumi Miyazaki
    第19回日本薬物動態学会年会(金沢) 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 洋充, 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
    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 顕, 宮崎 勝巳
    第21回日本TDM学会学術大会(大阪) 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]
    Mitsuru Sugawara, Mayumi Kitakubo, Yoh Takekuma, Vadivel Ganapathy, Katsumi Miyazaki
    Pharmaceutical Sciences World Congress(Kyoto) 2004年
  • Transport of ribavirin via nucleoside transporters in the trophoblast  [通常講演]
    Takashi Morita, Yoh Takekuma, Mitsuru Sugawara, Katsumi Miyazaki
    Pharmaceutical Sciences World Congress(Kyoto) 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
  • 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
  • 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
  • 循環器科病棟において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
  • 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
  • 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
  • 移植患者におけるタクロリムスと抗真菌剤との相互作用  [通常講演]
    中村浩規, 武隈 洋, 井上和幸, 岸川幸生, 菱沼隆則, 水柿道直, 岡田克典, 近藤丘, 大河内信弘, 里見進
    第19回日本TDM学会学術大会(熊本) 2002年
  • 日本人におけるCYP2B6及びCYP3A5遺伝子の多型解析  [通常講演]
    武隈 洋, 平塚真弘, 遠藤尚美, 奈良原香織, Samar Ismail Hamdy, 岸川幸生, 松浦正樹, 我妻恭行, 井上智子, 水柿道直
    日本薬学会第122年会(千葉) 2002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
  • 遺伝子多型診断による副作用発現の回避システム  [通常講演]
    岸川幸生, 平塚真弘, 武隈 洋, 松浦正樹, 我妻恭行, 奈良原香織, 水柿道直
    第9回クリニカルファーマシーシンポジウム(熊本) 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
  • 生体肝移植患者における持続血液濾過透析(CHDF)施行時のタクロリムスおよび抗真菌剤の血中動態  [通常講演]
    越浪由加, 須田範行, 武隈 洋, 小林道也, 岸野吏志, 宮崎勝巳, 森本祐二, 丸藤哲, 大村孝志
    第17回日本TDM学会学術大会(仙台) 2000年
  • 生体肝移植患者におけるタクロリムスの体内動態  [通常講演]
    小野尚志, 須田範行, 武隈 洋, 岸野吏志, 井関 健, 宮崎勝巳, 大村孝志, 岸田明博, 古川博之, 藤堂省
    日本薬学会第120年会(岐阜) 2000年
  • 抗癌剤溶解後の安定性評価と注射薬混注業務における使用期限の設定  [通常講演]
    武隈 洋, 須田範行, 岸野吏志, 井関 健, 宮崎勝巳
    日本薬学会第120年会(岐阜) 2000年
  • 文書による薬剤情報提供への取り組み  [通常講演]
    武隈 洋, 沖洋充, 深井敏隆, 蔵田俊一, 榊原則寛, 清川真美, 駿河幸恵, 中島かおり, 川合真次, 宮本剛典
    日本薬学会第118年会(京都) 1998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
  • 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 シンポジウム・ワークショップパネル(公募)
  • 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

その他活動・業績

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    平井彩良, 蕪木素代子, 柏木仁, 佐藤夕紀, 今井俊吾, 杉森博行, 菅原満, 武隈洋 第34回北海道薬物作用談話会要旨集 2021年09月 [査読無し][通常論文]
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    野中美玖, 佐藤夕紀, 柏木仁, 今井俊吾, 武隈洋, 菅原満 第34回北海道薬物作用談話会要旨集 2021年09月 [査読無し][通常論文]
  • 乳剤化によるコエンザイムQ10の吸収改善が抗酸化作用に与える影響
    池田真由美, 横山さや香, 八巻義朗, 佐藤夕紀, 柏木仁, 今井俊吾, 武隈洋, 菅原満 第34回北海道薬物作用談話会要旨集 2021年09月 [査読無し][通常論文]
  • 吸収改善を目的とした乳剤化に適する薬物の物性の解明
    榎聡美, 佐藤夕紀, 柏木仁, 今井俊吾, 武隈洋, 菅原満 第34回北海道薬物作用談話会要旨集 2021年09月 [査読無し][通常論文]
  • 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 日本緩和医療学会 第3回北海道支部学術大会要旨集 2021年08月 [査読無し][通常論文]
  • ベンゾジアゼピン(BZD)系薬剤の母乳中濃度測定と乳汁移行評価パラメーターの算出
    西村あや子, 古堅彩子, 馬詰武, 北村聖花, 相馬まゆ子, 能代究, 武隈洋, 菅原満, 井関健, 小林正紀 第68回 北海道薬学大会要旨集 2021年05月 [査読無し][通常論文]
  • 希釈液に着目した液体製剤ゲムシタビン誘発性血管痛の軽減法の考案
    内山数貴, 齋藤佳敬, 坂本達彦, 菅野亮太, 小松嘉人, 武隈洋, 菅原満 第68回 北海道薬学大会要旨集 2021年05月 [査読無し][通常論文]
  • がんの多剤耐性を克服する新規エトポシド誘導体の探索
    山田隼大, 王子谷健太, 柏木仁, 佐藤夕紀, 今井俊吾, 宮地弘幸, 武隈洋, 菅原満 日本薬学会北海道支部第148回例会要旨集 2021年05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
  • リネゾリドの血中濃度モニタリングにより血小板減少を回避し、治療が奏功した1例
    鏡圭介, 大聖貴之, 山﨑浩二郎, 石黒信久, 遠藤努, 高畑雅彦, 武隈洋, 菅原満 第33回北海道TDM研究会 研究発表会 2019年11月16日 [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]
  • 門脈およびリンパ管への薬物移行を考慮した消化管吸収の評価
    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]
  • エンテロイドを用いた薬物排出トランスポーターの機能解析
    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]
  • Xenopus laevis oocytesを用いたNiemann-Pick C1-Like 1(NPC1L1)発現系の最適化
    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]
  • 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]
  • 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]
  • 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, 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]
  • Continuous cytotoxic effects of BCR-ABL tyrosine kinase inhibitors (TKIs) after washout in human leukemic K562 cells.
    Aoyama T, Takekuma Y, Sumi M, Sato Y, Sugawara M 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology 2017年09月 [査読無し][通常論文]
  • ルテインの製剤化による消化管吸収改善
    定村樹, 佐藤夕紀, 梨本俊亮, 鷲見正人, 武隈洋, 菅原満 日本薬学会北海道支部第144 回例会 2017年05月 [査読無し][通常論文]
  • 実務実習前後における薬学生のRIASによるコミュニケーション分析
    森 綾子, 武隈 洋, 小林正紀, 山田勇磨, 佐藤夕紀, 鳴海克哉, 古堅彩子, 菅原 満 総合技術研究会2017東京大学 2017年03月08日 [査読無し][通常論文]
  • オキサ酸を乳化剤として用いたCoenzyme Q10の乳剤化と消化管吸収改善
    横山 さや香, 宮下 真美, 佐藤 夕紀, 武隈 洋, 丸山 真吾, 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]
  • 植村 真衣, 松井 耕平, 桑原 智希, 渡邉 瑞貴, 福田 隼, 加藤 七海, 武隈 洋, 菅原 満, 周東 智 日本薬学会年会要旨集 137年会 (2) 120 -120 2017年03月 [査読無し][通常論文]
  • 宮下 真美, 横山 さや香, 佐藤 夕紀, 武隈 洋, 吉田 英人, 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]
  • 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]
  • 助畑 歩, 武隈 洋, 鷲見 正人, 佐藤 夕紀, 菅原 満 日本薬学会年会要旨集 137年会 (4) 66 -66 2017年03月 [査読無し][通常論文]
  • 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-ラットおよびヒト血漿中濃度推移からのアプローチ-
    梨本俊亮, 佐藤夕紀, 鷲見正人, 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]
  • ダサチニブの週2回投与で分子遺伝学寛解に達成した一症例
    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]
  • 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]
  • テアニン錠剤(速放錠・徐放錠)の溶出性および吸収性の変動要因
    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 日本薬学会北海道支部第143 回例会 2016年05月 [査読無し][通常論文]
  • 医療薬学ブラッシュアップ講座 EBM入門(4)
    武隈洋 道薬誌 33 (4) 18 -22 2016年04月 [査読有り][通常論文]
  • 医療薬学ブラッシュアップ講座 EBM入門(3)
    武隈洋 道薬誌 33 (3) 11 -16 2016年03月 [査読無し][招待有り]
  • 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]
  • 医療薬学ブラッシュアップ講座 EBM入門(2)
    武隈洋 道薬誌 33 (2) 13 -21 2016年02月 [査読有り][通常論文]
  • α-トコフェロールの吸収動態に及ぼすエゼチミブの影響
    佐藤夕紀, 梨本俊亮, 武隈洋, 菅原満 第27回ビタミンE研究会 2016年01月08日 [査読無し][通常論文]
  • 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
  • 医療薬学ブラッシュアップ講座 EBM入門(1)
    武隈 洋 道薬誌 33 (1) 37 -41 2016年01月 [査読無し][招待有り]
  • イマチニブのTDM により副作用軽減と治療継続が可能となった二重癌の一 症例
    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 第29回北海道TDM研究会研究発表会 2015年12月05日 [査読無し][通常論文]
  • テアニン製剤(速放錠・徐放錠)を用いた溶出性および吸収性の検討
    山口和奎, 佐藤夕紀, 武隈 洋, 中川公太, 大野智弘, 本城政稔, 菅原 満 第29回北海道薬物作用談話会 2015年08月09日 [査読無し][通常論文]
  • 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
    石坂 悠, 武隈 洋, 平野 卓哉, 野田 敏宏, 熊井 恵美, 菅原 満 日本医薬品情報学会総会・学術大会講演要旨集 18回 73 -73 2015年06月 [査読無し][通常論文]
  • 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
    武隈 洋, 田澤 佑基, 臼窪 一平, 高田 一輝, 柴山 良彦, 重松 明男, 笠師 久美子, 豊嶋 崇徳, 井関 健, 菅原 満 臨床薬理の進歩 (36) 142 -152 2015年06月 [査読無し][通常論文]
     
    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。
  • 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
    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16日 [査読無し][通常論文]
  • 菅原 満, 武隈 洋, 柴山 良彦, 井関 健 医薬ジャーナル 51 (5) 1381 -1385 2015年05月 [査読無し][通常論文]
     
    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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    梨本 俊亮, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬剤学会年会講演要旨集 30年会 131 -131 2015年05月 [査読無し][通常論文]
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    佐藤 夕紀, 竹川 悠人, 能登 数馬, 武隈 洋, 菅原 満 日本薬剤学会年会講演要旨集 30年会 136 -136 2015年05月 [査読無し][通常論文]
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    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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    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29日 [査読無し][通常論文]
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    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]
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  • 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]
  • 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]
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    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]
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    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]
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    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]
  • 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]
  • 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]
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    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 [査読無し][通常論文]
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    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]
  • 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]
  • 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]
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    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]
  • 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]
  • 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]
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    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 [査読無し][通常論文]
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    堀田雄也, 川守田渉, 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135回例会(札幌) 2010年11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]
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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]
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    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]
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    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]
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    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]
  • 三浦正義, 阿知波一人, 下田直彦, 武隈洋, 原田浩 臨床薬理の進歩 (30) 106 -117 2009年07月10日 [査読無し][通常論文]
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  • 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]
  • 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]
  • テアニンの消化管吸収に関与するトランスポーター
    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 [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]
  • 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]
  • 小松 幹, 高畑 雅彦, 武隈 洋, 菅原 満, 加藤 貴志, 入江 徹, 安倍 雄一郎, 伊東 学, 三浪 明男 日本整形外科学会雑誌 82 (8) S1248 -S1248 2008年08月 [査読無し][通常論文]
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    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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    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]
  • 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]
  • 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]
  • 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]
  • 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]
  • リネゾリドの椎間板への移行性
    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 第21回北海道TDM研究会(札幌) 2007年 [査読無し][通常論文]
  • 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
  • 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]
  • 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]
  • 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]
  • タクロリムス血中濃度モニタリングのための採血法とその有用性の検討
    岩見大基, 堀田記世彦, 下田直彦, 森田 研, 野々村克也, 武隈 洋 第24回北海道腎移植談話会(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]
  • 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]
  • Y Watarai, K Morita, N Fukuzawa, K Nonomura, Y Takekuma, K Yamazaki, H Takada, K Miyazaki AMERICAN JOURNAL OF TRANSPLANTATION 5 186 -186 2005年05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]
  • 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]
  • 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
    國木賢一, 山本 崇, 武隈 洋, 菅原 満, 宮崎勝巳 日本薬学会北海道支部第124回例会 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]
  • 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]
  • 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]
  • 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]
  • 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]
  • 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
    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, 橋本聡一, 森本裕二 第18回北海道TDM研究会 研究発表会(札幌) 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
  • 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]
  • 消化管内の生理的条件を考慮した薬物消化管吸収評価系の構築 プロドラッグの吸収評価
    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]
  • 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]
  • 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]
  • 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]
  • 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
    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 [査読無し][通常論文]
  • 日本人におけるCYP2B6及びCYP3A5遺伝子の多型解析
    武隈 洋, 平塚 真弘, 遠藤 尚美, 奈良原 香織, Hamdy Samar Ismail, 岸川 幸生, 松浦 正樹, 我妻 恭行, 井上 智子, 水柿 道直 日本薬学会年会要旨集 122年会 (4) 17 -17 2002年03月 [査読無し][通常論文]
  • 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
  • 院内製剤の安定性と使用期限に関する検討
    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]
  • 岸川幸生, 平塚真弘, 武隈洋, 松浦正樹, 我妻恭行, 奈良原香織, 水柿道直 医療薬学フォーラム講演要旨集 9th 2001年
  • 沖 洋充, 山本 利花, 武隈 洋, 榊原 則寛, 小林 道也, 深井 敏隆, 荻野 修, 井関 健, 遠藤 晃, 櫻井 恒太郎, 宮崎 勝巳 日本病院薬学会年会講演要旨集 8 (0) 276 -276 1998年08月17日 [査読無し][通常論文]
  • 北大病院における薬剤情報提供
    中島かおり, 武隈 洋, 沖 洋充, 清川真美, 榊原則寛, 蔵田俊一, 深井敏隆, 川合真次, 宮本剛典, 小林道也, 荻野 修, 井関 健, 宮崎勝巳 北海道病院薬剤師会誌 55 41 -45 1998年 [査読無し][通常論文]

特許

  • 特願2017-40896:吸収促進剤およびその利用  2017年03月03日
    菅原満, 佐藤夕紀, 武隈洋, 丸山真吾
  • 特願2017-011816:テアニンの吸収性が改善された組成物  2017年01月26日
    佐藤夕紀, 武隈洋, 菅原満, 櫻田剛史, 中川公太, 本城政稔

受賞

  • 日本薬学会北海道支部 医療薬学貢献賞 教育部門
     6年制薬学教育に係る基盤構築 
    受賞者: 武隈 洋

共同研究・競争的資金等の研究課題

  • オキサゾリジノン系抗MRSA薬の唾液中濃度による治療モニタリングと投与量最適化
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 武隈 洋, 佐藤 夕紀, 今井 俊吾
  • 小腸上皮における薬物輸送解析のためのエンテロイドを用いた新規手法の確立
    日本学術振興会:科学研究費助成事業(学術研究助成基金助成金)基盤研究C一般
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 菅原 満
  • 高齢者の薬物投与量設計に必要な加齢による腎機能および薬物代謝能の定量的評価
    公益財団法人長寿科学振興財団:長寿科学研究者支援事業
    研究期間 : 2017年06月 -2018年03月 
    代表者 : 武隈 洋
  • 造血幹細胞移植時の抗がん薬併用療法における薬物投与順序の最適化
    日本学術振興会:科学研究費助成事業(学術研究助成基金助成金)基盤研究C一般
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 菅原 満
  • 抗がん剤併用療法時の薬物暴露順序の影響
    臨床薬理研究振興財団:研究奨励金
    研究期間 : 2012年04月 -2014年03月 
    代表者 : 武隈 洋
  • 生細胞内におけるUGT分子種の発現量比変動時の抱合活性および基質特異性変動の評価
    日本学術振興会:科学研究費助成事業(学術研究助成基金助成金)若手研究(B)
    研究期間 : 2012年04月 -2014年03月 
    代表者 : 武隈 洋
  • カルベジロールのグルクロン酸抱合反応に及ぼすエナンチオマー間の相互作用の解明
    栗林育英学術財団:研究助成
    研究期間 : 2010年04月 -2011年03月 
    代表者 : 武隈 洋
  • ミコフェノール酸の体内動態に及ぼす代謝酵素および排出蛋白の遺伝子多型の影響
    秋山記念生命科学振興財団:奨励助成
    研究期間 : 2006年04月 -2007年03月 
    代表者 : 武隈 洋
  • 抗癌剤投与プロトコールデータベース及び処方監査システムの構築
    日本学術振興会:科学研究費補助金(奨励研究)
    研究期間 : 2004年04月 -2005年03月 
    代表者 : 武隈 洋

教育活動情報

主要な担当授業

  • 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
  • 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
  • 医薬品情報学
    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 : 医薬品情報、薬剤疫学、医療情報、Evidence-based medicine (EBM)

大学運営

委員歴

  • 2020年04月 - 現在   医薬品相互作用研究会   評議委員
  • 2018年07月 - 現在   日本病院薬剤師会   編集委員
  • 2018年04月 - 現在   北海道薬剤師会   臨床・疫学研究倫理審査委員
  • 2017年04月 - 現在   日本医療薬学会   代議員
  • 2016年07月 - 現在   日本医薬品情報学会   教育検討委員会 委員
  • 2015年05月 - 現在   日本TDM学会   評議委員
  • 2014年06月 - 現在   日本TDM学会   広報委員会委員
  • 2010年 - 現在   北海道TDM研究会   幹事   北海道TDM研究会
  • 2010年04月 - 2020年06月   北海道薬剤師会   学術・情報委員会
  • 2016年03月 - 2018年06月   日本病院薬剤師会   地域編集委員

社会貢献活動

  • 平成21年度 北海道医療大学 生涯学習事業 感染制御専門薬剤師養成基礎講座
    期間 : 2009年08月19日
    役割 : 講師
    主催者・発行元 : 北海道医療大学


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