研究者基本情報

• 博士（薬学）, 北海道大学

• https://researchmap.jp/read0209214

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901045800993263

• 200901045800993263

• 生物系薬学
• 医療系薬学

• 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

• 修士課程, 生命科学院
• 博士課程, 生命科学院

研究活動情報

• 2023年03月, 日本薬学会, The Most Published Author Award 2018-2022 in BPB
  武隈 洋
• 2014年05月, 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
  武隈 洋

• Linezolid-Induced Serotonin Release from QGP-1 Cells.
  Takezo Tsutsumi; Hitoshi Kashiwagi; Shungo Imai; Yuki Sato; Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  Drug research, 2026年03月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, Nausea and vomiting are commonly reported side effects of long-term linezolid therapy, which is indispensable for tuberculosis and osteoarticular infections. Since the mechanism underlying the development of nausea and vomiting during linezolid treatment is unknown, this study aimed to explore the mechanisms by focusing on the monoamine oxidase-inhibiting effect of linezolid.In vitro serotonin release assays were performed using QGP-1 cells as a surrogate for enterochromaffin cells exposed to linezolid, the monoamine oxidase inhibitor clorgyline, and the known emetogenic agent cisplatin. Serotonin concentrations in the solutions were measured using an enzyme-linked immunosorbent assay. Clorgyline and cisplatin were administered simultaneously with linezolid to elucidate the serotonin release mechanism and confirm the synergistic effects. The intracellular Ca2+assays using Fura‑2 were also performed to assess whether serotonin release is mediated by Ca2+‑dependent exocytosis.Linezolid exposure significantly increased serotonin release from QGP-1 cells in concentration- and time-dependent manners. Serotonin release also increased in the clorgyline exposure group, and the release of serotonin in the linezolid/clorgyline co-exposure group was higher than that in the single-exposure groups. In contrast, no significant serotonin release or synergistic effects were observed in the cisplatin/linezolid-exposed groups. The Ca2+assays demonstrated that linezolid exposure did not change intracellular Ca2+levels.Serotonin release was observed when QGP-1 cells were exposed to linezolid, an effect similar to that observed with the potent monoamine oxidase A inhibitor clorgyline. Furthermore, the Ca2+assays indicated that linezolid‑induced serotonin release occurs independently of Ca2+‑dependent exocytosis.
• Impact of baseline regular magnesium oxide administration on chemotherapy-induced constipation during cisplatin-containing treatment.
  Yoshitaka Saito; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  International journal of clinical oncology, 31, 2, 336, 346, 2026年02月, ［国内誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Chemotherapy-induced constipation frequently occurs with cisplatin-containing treatments, partly because of concomitant neurokinin 1 and serotonin 3 receptor antagonists. We have clinically observed that patients with baseline regular laxative administration, most of whom were on magnesium oxide, exhibited less chemotherapy-induced constipation than those without, and assessed its impact on symptom development in real-world cisplatin-containing treatment. METHODS: Patients with lung cancer receiving cisplatin-containing treatment (n = 240) were divided into a control group without baseline laxative administration and a magnesium group with baseline regular magnesium oxide administration and retrospectively evaluated. The primary endpoint was evaluation of the incidence of grade ≥ 2 constipation during the first 7 days following treatment initiation. RESULTS: Incidence of grade ≥ 2 constipation was 82.5% in the control group and 50.0% in the magnesium group, which was significantly less in the magnesium group (P < 0.0001). The incidence of all-grade symptoms was also significantly lower in the magnesium group than in the control group (67.5% vs. 84.5%, P = 0.02). Additionally, the administration of new laxatives was less common in the magnesium group (P = 0.007). Multivariable logistic regression analysis suggested that baseline administration of magnesium oxide is a preventive factor for grade ≥ 2 constipation. Furthermore, patients receiving 2 g daily magnesium oxide at baseline developed significantly less grade ≥ 2 constipation than those with < 2 g (19.1% and 84.2%, respectively, P < 0.0001). CONCLUSION: The present study suggests that patients with baseline regular magnesium oxide administration exhibit less chemotherapy-induced constipation than those without the administration in cisplatin-containing treatments.
• Evaluating the potential to predict chemotherapy-induced nausea and vomiting in carboplatin-containing treatment based on symptoms induced by prior cisplatin-containing treatment.
  Yoshitaka Saito; Takuya Watanabe; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Scientific reports, 16, 1, 5817, 5817, 2026年01月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, Chemotherapy-induced nausea and vomiting (CINV) is a serious adverse effect of cisplatin (CDDP)- and carboplatin (CBDCA)-containing treatments. In this study, we aimed to assess the potential to predict CINV in subsequent CBDCA-containing chemotherapy based on symptoms induced by prior CDDP-containing treatments. Patients with thoracic cancer who received CDDP followed by CBDCA treatments (n = 52) were divided into a control group, including patients with total control (TC) of CINV during prior CDDP-containing treatment period, and a CINV-experience group, including patients who did not achieve TC of CINV during the CDDP-containing treatment period. Patients were retrospectively evaluated. The TC rates during all evaluation periods (0-120 h) were significantly lower in the CINV-experience group than in the control group (45.5% and 86.7%, respectively, P = 0.002), which met the primary endpoint. The incidence rates of all-grade nausea and anorexia were also significantly higher in the CINV-experience group. In conclusion, our study suggests that CINV prediction in subsequent CBDCA-containing treatment based on the symptoms induced by prior CDDP-containing treatment is achievable.
• Preventive effect of hot compress on phlebitis during cisplatin and Vinorelbine treatment for non-small cell lung cancer.
  Osamu Taniguchi; Yoshitaka Saito; Tatsuhiko Sakamoto; Jun Sakakibara-Konishi; Yoh Takekuma; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 34, 2, 107, 107, 2026年01月19日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Vinorelbine (VNR) is a key chemotherapeutic agent for treating non-small cell lung cancer (NSCLC). However, peripheral venous administration frequently induces phlebitis in 20-50% of patients. A previous study showed that applying a hot compress during VNR was effective in patients who had already developed symptoms. Therefore, this method was applied to all patients receiving VNR via peripheral venous administration at Hokkaido University Hospital. Herein, we aimed to evaluate the prophylactic efficacy of hot compresses for VNR-induced phlebitis in real-world settings. METHODS: Patients with NSCLC who received cisplatin (CDDP) + VNR (n = 92) were retrospectively evaluated. Patients were divided into a hot compress group, which included patients who received hot compresses during VNR administration, and a control group that did not receive hot compresses. The primary endpoint was the frequency of phlebitis during the first cycle between the groups. RESULTS: Hot compress significantly reduced the frequency of phlebitis during the first cycle (47.3% and 18.9% in the control and hot compress groups, respectively; P = 0.008) and on day 8 of the first cycle (38.2% and 10.8%; P = 0.004), with primary endpoint accomplishment. Furthermore, symptom reduction using hot compresses was confirmed among patients who received VNR on day 8 via a different arm from that administered on day 1 (31.6% vs. 3.0%, P = 0.002). Additionally, the onset of the first occurrence of VNR-induced phlebitis was significantly delayed (P = 0.008). CONCLUSION: Hot compresses significantly reduced the frequency of VNR-induced phlebitis in patients with NSCLC receiving CDDP + VNR.
• Successful re-administration after nano-liposomal irinotecan-induced severe hypersensitivity reaction: a case report.
  Ryota Kanno; Yoshitaka Saito; Yoh Takekuma; Kazuaki Harada; Yoshito Komatsu; Mitsuru Sugawara
  Journal of pharmaceutical health care and sciences, 11, 1, 110, 110, 2025年12月22日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Nano-liposomal irinotecan (nal-IRI) combined with 5-fluorouracil (5-FU) and levofolinate has been reported to extend the survival of patients with pancreatic cancer and represents an effective second-line treatment. Nal-IRI encapsulates IRI in liposomes modified with polyethylene glycol (PEGylation), which can lead to infusion reactions. Hypersensitivity reactions (HSR) to chemotherapeutic agents include both allergic and infusion reactions, which are difficult to distinguish. Severe HSR can be fatal; however, discontinuation of the suspected drug directly affects the treatment strategy. We report a case of severe HSR during the first nal-IRI administration, in which treatment was successfully continued with supportive management. CASE PRESENTATION: A woman in her early 80s with metastatic pancreatic cancer received nal-IRI + 5-FU + levofolinate as second-line treatment. Five minutes after the initiation of the first nal-IRI infusion, the patient developed a tightening sensation in the head, respiratory distress, convulsions, and loss of consciousness, with percutaneous oxygen saturation dropping to the 80% range. The nal-IRI infusion was immediately discontinued, and emergency management was initiated with intravenous infusion of hydrocortisone, famotidine, d-chlorpheniramine maleate, and oxygen administration, resulting in symptom improvement. Given the limited treatment options for metastatic pancreatic cancer and the patient's strong desire to continue therapy, we decided to re-administer the regimen with intensified management, increasing dexamethasone to 19.8 mg and adding famotidine 20 mg and d-chlorpheniramine maleate 5 mg. Furthermore, we adopted a three-step dose-escalation method. The infusion was started at one-third of the standard rate, increased to two-thirds after 30 min, and finally adjusted to the full rate after another 30 min, after confirming the absence of HSR symptoms. Consequently, the patient did not exhibit any signs of HSR, and the same administration method was continued for 11 cycles until disease progression. CONCLUSIONS: The novelty of this report lies in presenting, for the first time, the detailed course and process by which treatment was successfully continued in a patient experiencing severe HSR upon initial nal-IRI administration, through enhanced supportive care tailored to the characteristics of the drug and stepwise dose adjustment.
• Evaluation of factors associated with clinically problematic hiccups in cisplatin-containing treatment with dexamethasone and neurokinin 1 receptor antagonists.
  Yoshitaka Saito; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  International journal of clinical oncology, 30, 12, 2504, 2511, 2025年12月, ［国内誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Chemotherapy-induced hiccups are one of the frequently appearing adverse events. Previous reports have suggested that cisplatin (CDDP) combined with dexamethasone and neurokinin 1 (NK1) receptor antagonists is particularly associated with these symptoms. Consequently, we aimed to identify additional factors involved in the development of problematic hiccups during the real-world treatment. METHODS: Patients with thoracic cancer first receiving CDDP-containing treatment (≥ 75 mg/m2) with dexamethasone, palonosetron, and aprepitant were retrospectively assessed (n = 286). The primary endpoint was the evaluation of risk factors for grade ≥ 2 hiccups during the first cycle. Secondary endpoints were the evaluation of factors for all-grade symptoms and the efficacy of rescue medication. RESULTS: The incidence of grade ≥ 2 hiccups was 32.9%, with all-grade symptoms of 44.8%. Grade 3 severe hiccups were observed in 5.2% of the patients. Most patients (96.8%) received metoclopramide as first-line treatment, and the efficacy of the first medication was confirmed in 59.6% of patients. Multivariate logistic regression analyses identified male sex, baseline hypoalbuminemia, and concomitant bevacizumab as significant risk factors for grade ≥ 2 problematic hiccups (adjusted odds ratio with 95% confidence interval 10.32 [4.38-24.32], P < 0.0001 for males; 2.41 [1.06-5.50], P = 0.04 for hypoalbuminemia; and 3.42 [1.25-9.36], P = 0.02 for concomitant bevacizumab). Moreover, male sex was identified as a singular risk factor for all-grade symptoms (7.94 [4.14-15.22], P < 0.0001). CONCLUSION: Our study revealed that male sex, hypoalbuminemia, and concomitant bevacizumab use were significant risk factors for clinically problematic hiccups in patients receiving CDDP-containing treatment along with dexamethasone and NK1 receptor inhibitors for thoracic cancer.
• Evaluation of factors associated with drug fever following gemcitabine and nanoparticle albumin-bound paclitaxel treatment for pancreatic cancer.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 11, 1006, 1006, 2025年11月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Gemcitabine (GEM) + nanoparticle albumin-bound paclitaxel (nab-PTX) is an effective treatment for advanced pancreatic cancer. However, drug fever is a frequently observed adverse effect of GEM, and PTX can also induce symptoms. This study aimed to identify factors for drug fever in the real-world treatment of pancreatic cancer with GEM + nab-PTX. METHODS: We retrospectively assessed patients with pancreatic cancer who received GEM + nab-PTX (n = 386). The primary endpoint was the identification of factor(s) associated with the incidence of drug fever following the first administration. We also assessed symptoms between specific patient groups. RESULTS: The incidence of drug fever following the first GEM + nab-PTX treatment was 12.7%. The median onset time was day 3 (range: 1-4) with a symptom duration of 1 (1-6) day. Unresectable setting (adjusted odds ratio [95% confidence interval]: 3.35 [1.35-8.32], P = 0.009) and elevated baseline C-reactive protein (CRP) levels (≥ 1.0 mg/dL) (3.55 [1.80-6.98], P = 0.0002) were identified as risk factors using the multivariable logistic regression analysis. Patients receiving regular antipyretic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and/or acetaminophen had a lower risk (0.42 [0.20-0.87], P = 0.02). No difference was observed in the impact of the type of antipyretics on drug fever between NSAIDs and acetaminophen. CONCLUSION: An unresectable disease status and high baseline CRP levels are risk factors for drug-induced fever, while patients receiving regular antipyretics are at lower risk of developing these symptoms during real-world treatment of pancreatic cancer with GEM + nab-PTX.
• Baseline hypoalbuminemia enhances regorafenib-induced problematic fatigue development in real-world metastatic colorectal cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 11, 990, 990, 2025年10月29日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Regorafenib, a multikinase inhibitor for treating metastatic colorectal cancer (mCRC), induces fatigue in 40-50% of administered patients, including approximately 10% of grade ≥ 3 cases. Additionally, hypoalbuminemia is associated with cancer- and chemotherapy-induced fatigue and frequently observed in patients with advanced cancers. This study aimed to assess the impact of baseline hypoalbuminemia on the development of clinically problematic fatigue in a real-world regorafenib treatment for mCRC. METHODS: Patients with mCRC who underwent regorafenib (n = 102) were divided into the control (baseline serum albumin levels ≥ 3.5 g/dL) and hypoalbuminemia (baseline serum albumin levels < 3.5 g/dL) groups, and retrospectively evaluated. The primary endpoint was comparison of grade ≥ 2 fatigue incidence during all treatment cycles. We also assessed the impact of grade ≥ 2 symptoms on the treatment efficacy. RESULTS: Incidence of grade ≥ 2 fatigue in all treatment cycles in the hypoalbuminemia group was 41.7%, which was significantly higher than that in the control group (14.1%, P = 0.008). In addition, grade ≥ 2 fatigue within the first cycle was significantly more confirmed in the hypoalbuminemia group than in the control group (37.5% vs. 11.5%, P = 0.01). Additionally, patients with early grade ≥ 2 fatigue within 14 days from treatment initiation had a significantly shorter time to treatment failure or overall survival than those without the symptoms. CONCLUSION: Patients with baseline hypoalbuminemia developed clinically problematic fatigue after regorafenib monotherapy for mCRC. Because regorafenib is a later-line mCRC treatment, successful management of emerging fatigue is crucial and requires further evaluation.
• Factors associated with taxane-associated acute pain syndrome in pancreatic cancer patients receiving gemcitabine and nab-paclitaxel.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Discover oncology, 16, 1, 1967, 1967, 2025年10月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Taxane-associated acute pain syndrome (T-APS) is a common adverse event in patients treated with gemcitabine (GEM) + nanoparticle albumin-bound paclitaxel (nab-PTX) for pancreatic cancer. As several T-APS risk factors, such as age, cancer type, and taxane dose or formulation, differ between pancreatic cancer and other malignancies in previous studies, we aimed to identify factors associated with T-APS in a real-world setting of GEM + nab-PTX treatment for pancreatic cancer. METHODS: We retrospectively analyzed 394 patients with pancreatic cancer receiving GEM + nab-PTX. The primary endpoint was the identification of factors associated with all-grade T-APS. Symptom incidence was also compared across specific patient groups. RESULTS: T-APS occurred in 26.1% of patients after the first GEM + nab-PTX administration (grade 1: 21.6%; grade 2: 4.6%). Among patients with T-APS, 39.8% received medication, with more than two-thirds reporting symptom relief. Multivariable logistic regression analyses identified body mass index (BMI) ≥ 25 kg/m2 as a risk factor and baseline use of mild analgesics (non-steroidal anti-inflammatory drugs [NSAIDs] and/or acetaminophen) as a preventive factor (adjusted odds ratio, 2.98; 95% confidence interval, 1.68-5.31; P = 0.0002 for BMI, 0.48; 0.26-0.89; P = 0.02 for mild analgesics). A subgroup analysis comparing baseline NSAIDs and acetaminophen in patients receiving mild analgesic monotherapy showed no significant difference (P = 0.49). CONCLUSION: Our study identified BMI ≥ 25 kg/m2 as a risk factor and baseline use of mild analgesics as a preventive factor for T-APS development in a real-world GEM + nab-PTX regimen for pancreatic cancer.
• Impact of baseline hypoalbuminemia on peripheral edema induced by gemcitabine and nab-paclitaxel for pancreatic cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 11, 938, 938, 2025年10月13日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Gemcitabine (GEM) + nanoparticle albumin-bound paclitaxel (nab-PTX), which is effective in treating pancreatic cancer, frequently induces peripheral edema. Hypoalbuminemia causes generalized peripheral edema and occasionally occurs in patients with cancer, but reports evaluating its interaction with chemotherapy-induced symptoms are lacking. Therefore, we aimed to assess the effect of baseline hypoalbuminemia on peripheral edema following real-world GEM + nab-PTX therapy. METHODS: Patients with pancreatic cancer receiving GEM + nab-PTX (n = 212) were divided into a hypoalbuminemia group (serum albumin levels < 3.5 g/dL), and a control group without hypoalbuminemia, and retrospectively evaluated. The primary endpoint was the incidence of grade ≥ 2 peripheral edema within 6 months of treatment initiation. RESULTS: The incidence of grade ≥ 2 peripheral edema within 6 months was 5.7% in the control group and 22.6% in the hypoalbuminemia group, with a significant difference (P = 0.0009), meeting the primary endpoint. The onset time of grade ≥ 2 peripheral edema was significantly earlier in the hypoalbuminemia group than in the control group (P = 0.0003). In contrast, the incidence of all-grade symptoms was 20.1% in the control group and 30.2% in the hypoalbuminemia group, which was not significantly different (P = 0.13). These results were confirmed in the propensity score-matched population. Multivariate Cox proportional hazard regression analyses showed that baseline hypoalbuminemia was a significant risk factor for grade ≥ 2 peripheral edema (adjusted hazard ratio, 3.84; 95% confidence interval, 1.60-9.23; P = 0.003). CONCLUSION: Our study revealed that patients with baseline hypoalbuminemia who received GEM + nab-PTX therapy for pancreatic cancer developed problematic peripheral edema.
• Younger age as a risk factor for rash development in pemetrexed and carboplatin treatment with dexamethasone prophylaxis.
  Yoshitaka Saito; Osamu Taniguchi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 11, 932, 932, 2025年10月11日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Carboplatin (CBDCA) plus pemetrexed (PEM) is one of the most effective regimens for treating thoracic cancer. Rash, which is mainly caused by PEM, occurs in 15-30% of patients. Dexamethasone administration for 3 days is recommended to manage rash, chemotherapy-induced nausea, and vomiting in this regimen. However, the nature of the PEM-induced rashes is not fully understood. Consequently, we aimed to identify the risk factors associated with rash development under dexamethasone prophylaxis in CBDCA + PEM treatment. METHODS: Patients with thoracic cancer who underwent CBDCA + PEM treatment (n = 133) were retrospectively assessed. The primary endpoint of the present study was to identify the risk factor(s) for the incidence of all-grade rash in the first cycle. Factors affecting the incidence during all treatment cycles were also evaluated. RESULTS: The incidence of all-grade rash in the first cycle was 24.1%, including 16.5% for grade 1, 5.3% for grade 2, and 2.3% for grade 3, respectively. Moreover, that in all cycles, it was 27.1%, with 18.8% for grade 1, 6.0% for grade 2, and 2.3% for grade 3. Multivariate logistic regression analyses identified that age < 65 years was the singular independent risk factor for rash development in the first and all cycles (adjusted odds ratio, 2.79; 95% confidence interval, 1.17-6.67; p = 0.02 for the first cycle, 3.03, 1.29-7.09; p = 0.01 for all cycles). CONCLUSION: Our study revealed that patients aged < 65 years were at a significantly higher risk of rash development during CBDCA + PEM chemotherapy with dexamethasone prophylaxis than patients ≥ 65 years of age.
• Temporal effects of empirical round-up of serum creatinine on the accuracy of estimated kidney function after critical illness.
  R Mikami; S Imai; M Hayakawa; H Kashiwagi; Y Sato; S Nashimoto; M Sugawara; Y Takekuma
  Die Pharmazie, 80, 9, 93, 101, 2025年10月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, This study aimed to evaluate the temporal effect of a serum creatinine (SCr) correction intervention in critically ill patients with daily muscle wasting. A total of 5,355 critical care days in 574 patients with creatinine clearance (Clcr) and glomerular filtration rate (GFR) measured and estimated simultaneously were included. The primary endpoint was the difference in accuracy over time of the estimated Clcr/GFR relative to the measured Clcr. The CG equation was used to estimate Clcr, and the MDRD and CKD-EPI-equations were used to estimate GFR. Estimated Clcr(round-up)/GFR(round-up) indicates the estimated Clcr/GFR calculated using the rounded up value if SCr was <0.6 mg/dL. Bias was analyzed using Bland-Altman analysis, correlation using Spearman's rank correlation coefficient, and accuracy using percentage within 30% of the measured Clcr (P30). The CKD-EPI equation showed a large underestimation bias in the early period, whereas the CG and MDRD equations indicated large overestimation biases in the later period. Round-up correction increased the underestimation bias in the early period of the CG(round-up) and MDRD(round-up) equations, but decreased the overestimation bias in the later period. The limits of agreements for the CG(round-up) and MDRD(round-up) equations were narrower, although not consistently acceptable. The correlations were stronger for the CG(round-up) and MDRD(round-up) equations. Accuracy did not improve with the corrective intervention. Conclusion: SCr round-up correction increased the underestimation of kidney function in the early phase, but mitigated overestimation in the later phase. The limits of agreement remained unacceptable, and the accuracy did not improve.
• 未分画ヘパリンモニタリングにおけるAPTTと抗Xa活性の不一致に対する腎機能の影響 探索的後ろ向き観察研究
  三上 龍生; 早川 峰司; 今井 俊吾; 斉藤 智誉; 佐藤 夕紀; 柏木 仁; 梨本 俊亮; 菅原 満; 武隈 洋
  日本腎臓病薬物療法学会誌, 14, 特別号, S172, S172, (一社)日本腎臓病薬物療法学会, 2025年09月
  日本語
• Celecoxib has less aggravating effect on cisplatin-induced nephrotoxicity in comparison with non-selective cyclooxygenase inhibitors: a retrospective multi-institutional study.
  Keisuke Okamoto; Yoshitaka Saito; Kenta Takahashi; Yoh Takekuma; Jun Sakakibara-Konishi; Katsuya Narumi; Mitsuru Sugawara; Masaki Kobayashi
  International journal of clinical oncology, 30, 9, 1757, 1763, 2025年09月, ［国内誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Cisplatin (CDDP)-induced nephrotoxicity (CIN) is one of its most serious adverse effects. Although we previously demonstrated that celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, attenuates CIN in a basic study, there are no reports that have evaluated its clinical impact on CIN. Therefore, we aimed to determine the effect of celecoxib on CIN compared with that of non-selective COX inhibitors. METHODS: Patients with lung cancer receiving CDDP (≥ 60 mg/m2)-containing regimens with regular administration of loxoprofen or naproxen (COX-1 group), or celecoxib were evaluated in this retrospective, multi-institutional study. The primary endpoint was the evaluation of CIN incidence in all treatment cycles between the groups. In addition, the variance in creatinine clearance (CCr) and the incidence of gastrointestinal adverse effects were evaluated. RESULTS: CIN occurred in 24.2% of patients in the COX-1 group (n = 33) and 0% of those in the celecoxib group (n = 15) in all cycles, showing a significant difference (P = 0.04). In addition, the variance in CCr was significantly smaller in the celecoxib group than in the COX-1 group in all cycles, as well as at the primary endpoint (P = 0.02). However, there was no difference in the incidence of CIN or variance in CCr in the first cycle between the two groups. The incidences of nausea, vomiting, and anorexia were similar between the groups, implying a similar amount of oral hydration. CONCLUSION: These findings suggest that celecoxib is less aggravating on CIN than non-selective COX inhibitors.
• Temporal effects of errors in estimating kidney function after critical illness on drug dosing categories.
  Ryusei Mikami; Shungo Imai; Mineji Hayakawa; Kento Sabashi; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  British journal of clinical pharmacology, 2025年08月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, AIMS: This study aimed to clarify how the trajectories of the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations differ from measured creatinine clearance (Clcr) and to determine their impact on drug dosing categories in critically ill patients. METHODS: We used data from 5355 days following critical illness to estimate the trajectories of the above-mentioned kidney function equations using a linear mixed model. In addition, we determined whether the CG, MDRD and CKD-EPI equations would change drug dosing categories (<15, 15-29, 30-59, 60-89, 90-119, 120-149, or ≥150 mL/min) over time compared with that observed using measured Clcr. RESULTS: The rate of change relative to baseline in measured Clcr remained almost unchanged during the 28 days of observation (-0.02 [95% confidence interval, CI: -0.19-0.14] mL/min/1.73 m2/day). In contrast, all indirect kidney function estimating equations showed a time-dependent increase in the rate of change, which was largest for the CG equation, followed by the MDRD and CKD-EPI equations (+2.00 [95% CI: 1.89-2.12], +1.50 [95% CI: 1.34-1.67] and +0.77 [95% CI: 0.61-0.93] mL/min/1.73 m2/day, respectively). More than half of the CG, MDRD and CKD-EPI equations showed discrepancies with the measured Clcr and drug dosing categories, with underestimation in the early phases and overestimation in the later phases being more common. CONCLUSION: Creatinine-based indirect kidney function estimation equations increased over time, indicating erroneous drug dosing categories on over half of the critical care days.
• The effect of sacubitril/valsartan on urinary C-peptide excretion and endogenous insulin secretory capacity in a patient with type 2 diabetes: a case report.
  Shun Onodera; Masashi Miyamae; Issei Higuchi; Shunsuke Nashimoto; Akinobu Nakamura; Mitsuru Sugawara; Yoh Takekuma
  Journal of pharmaceutical health care and sciences, 11, 1, 75, 75, 2025年08月17日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The evaluation of endogenous insulin secretory capacity is important in the selection of diabetes treatment. C-peptide, which is secreted in equivalent amounts as insulin, is a versatile test for this evaluation. Urinary C-peptide is widely used because it is less invasive. Sacubitril/valsartan, used to treat hypertension and chronic heart failure, has been reported to increase urinary C-peptide levels; however, its effect on endogenous insulin secretion remains unknown. In this report, we present a case in which insulin secretory capacity was evaluated according to a glucagon stimulation test in addition to urinary C-peptide levels in a patient receiving sacubitril/valsartan. CASE PRESENTATION: A male patient in his 50s with type 2 diabetes and hypertension, without renal dysfunction, was treated with sacubitril/valsartan. The results of the glucagon stimulation test showed a C-peptide change of 2.28, and the C-peptide index on the same day was 1.25, indicating normal endogenous insulin secretory capacity. In contrast, 24-h urinary C-peptide excretion was abnormally high at 615.2 µg/day. After discontinuation of sacubitril/valsartan, urinary C-peptide excretion decreased over time (615.2 to 369.0 µg/day), but blood glucose levels did not increase during this period. CONCLUSIONS: In this case, 24-h urinary C-peptide excretion was abnormally elevated despite preserved endogenous insulin secretory capacity, as assessed by the glucagon stimulation test. Although this observation is based on a single case and cannot be generalized, it suggests that sacubitril/valsartan may interfere with the interpretation of urinary C-peptide levels. Therefore, in such clinical contexts, dynamic tests such as the glucagon stimulation test may serve as a useful adjunct to avoid potential overestimation of insulin secretory capacity when relying solely on urinary C-peptide levels.
• Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin-bilirubin (ALBI) score of patients with liver dysfunction.
  Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 31, 8, 102766, 102766, 2025年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Voriconazole (VRCZ) is an antifungal agent used to treat refractory fungal infections. Its dosage is adjusted based on the individual liver function. In this study, we aimed to establish a population pharmacokinetic analysis model based on the albumin-bilirubin (ALBI) score to objectively assess the liver function using only albumin and total bilirubin levels as covariates. METHODS: In total, 126 plasma samples of 16 patients with liver dysfunction who received oral VRCZ between 2012 and 2022 were analyzed in this study. Phoenix NLME software was used for population pharmacokinetic analysis, and Monte Carlo simulations were performed to determine the optimal dosing regimen to achieve the target blood VRCZ concentration. RESULTS: Blood VRCZ concentration was described using a one-compartment model with lag time. In the final model, objective function was significantly decreased upon ALBI score incorporation into clearance. Monte Carlo simulations showed that the optimal dosing schedules were 100 mg twice daily, 75 mg twice daily, and 50 mg twice daily for ALBI scores of -3, -2, and -1, respectively. Notably, for an ALBI score of 0, target blood VRCZ concentration was exceeded, even a dosing regimen of 50 mg twice daily. CONCLUSION: To the best of our knowledge, this study is the first to incorporate the ALBI score into a population pharmacokinetic model for VRCZ. Our simulation results suggest that the maintenance dose should be reduced based on the ALBI score. Furthermore, our findings highlight the potential use of the ALBI score for optimal drug dosage design.
• Temporary hypocalcemia induced by cetuximab sarotalocan without hypomagnesemia in a patient with hypoparathyroidism: a novel case report.
  Moeko Kado; Yoshitaka Saito; Tatsuhiko Sakamoto; Takayoshi Suzuki; Yoh Takekuma; Mitsuru Sugawara
  Journal of pharmaceutical health care and sciences, 11, 1, 58, 58, 2025年07月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Cetuximab sarotalocan, which utilizes the light-activatable dye IRDye700Dx conjugated with cetuximab, is a first-in-class drug based on photoimmunotherapy for treating recurrent head and neck squamous cell carcinoma. Cetuximab frequently induces hypomagnesemia and secondary hypocalcemia. Herein, we report a case of independent hypocalcemia without hypomagnesemia during treatment and discuss symptom progression. CASE PRESENTATION: A female patient with left epipharyngeal cancer, hypothyroidism, and hypoparathyroidism was treated with cetuximab and sarotalocan. On day 3, serum-adjusted calcium levels decreased from 9.6 to 7.4 mg/dL, increased to 8.2 mg/dL on day 9, and further increased to 8.8 mg/dL on day 27; serum magnesium levels were not evaluated. After the second administration, serum-adjusted calcium levels decreased two days later, fluctuating between 7.6 and 8.1 mg/dL for three weeks. Serum magnesium levels were within the normal range, with no significant variation detected during the second cycle. A similar symptom course was observed during the third cycle. The patient received enteral nutrition daily with 424.8-1,038.4 mg of calcium, with daily adjustment during the administration, except on day 2. She received peripheral intravenous nutrition for several days after tumor illumination. Concomitant medications did not appear to affect serum calcium levels. Considering the case process and previous reports, we hypothesized that concomitant hypoparathyroidism, in addition to reduced calcium intake due to the treatment, may have contributed to the observed reduction. CONCLUSIONS: Hypocalcemia without hypomagnesemia can occur in patients with hypoparathyroidism receiving near-infrared photoimmunotherapy with cetuximab sarotalocan. The precise mechanisms and epidemiological features warrant further investigations.
• Impact of baseline proteinuria on progression-free survival after regorafenib treatment for metastatic colorectal cancer.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 5, 443, 443, 2025年05月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Regorafenib improves the survival of patients with metastatic colorectal cancer (mCRC). However, proteinuria frequently occurs in regorafenib treatment, and development of severe hypertension, which is closely related to proteinuria, is associated with better treatment outcomes. We previously reported that patients with baseline proteinuria exhibit regorafenib-induced problematic symptoms. In this study, we aimed to assess the effect of baseline proteinuria on the treatment efficacy of regorafenib for mCRC. METHODS: Patients with mCRC receiving regorafenib (n = 100) were categorized into control (without baseline proteinuria) and pre-existing proteinuria (baseline grades 1-2) groups and retrospectively evaluated. The primary endpoint was the progression-free survival (PFS). RESULTS: Patients in the pre-existing proteinuria group exhibited significantly worse PFS than those in the control group (median with 95% confidence interval [CI] = 51 (46-56) and 56 (49-81) days, respectively; P = 0.04). Overall survival and disease control rate were lower in the pre-existing proteinuria group than in the control group although the difference was not statistically significant (P = 0.11 and 0.10, respectively). Similar results were obtained in the propensity score-matched population. Multivariate Cox hazard regression analyses revealed that baseline pre-existing proteinuria was associated with poor PFS (adjusted hazard ratio = 1.67; 95% CI = 1.03-2.72; P = 0.04). Additionally, ratio of drug suspension duration during all treatment cycles was higher in patients with pre-existing proteinuria than those without symptoms. CONCLUSION: Our results suggest that patients with baseline proteinuria experience poor PFS following regorafenib treatment for mCRC, although we should consider the clinical significance of the difference.
• イリノテカン誘発性コリン症状に対する抗コリン薬単回予防投与の症状コントロール不良因子の探索
  渡辺 拓也; 齋藤 佳敬; 武隈 洋; 清水 康; 木下 一郎; 小松 嘉人; 菅原 満
  日本臨床腫瘍薬学会雑誌, 41, 137, 137, (一社)日本臨床腫瘍薬学会, 2025年05月
  日本語
• 非小細胞肺がん患者におけるドセタキセル誘発性浮腫の要因分析
  山下 慎介; 齋藤 佳敬; 今井 俊吾; 柏木 仁; 佐藤 夕紀; 梨本 俊亮; 榊原 純; 清水 康; 木下 一郎; 武隈 洋; 菅原 満
  日本臨床腫瘍薬学会雑誌, 41, 139, 139, (一社)日本臨床腫瘍薬学会, 2025年05月
  日本語
• アミノ酸トランスポーターSNAT4を介したエンドサイトーシスによる基質修飾リポソームの取り込み
  松山 琳空; 佐藤 夕紀; 藤田 聡; 丸山 真吾; 梨本 俊亮; 柏木 仁; 武隈 洋; 菅原 満
  日本薬剤学会年会講演要旨集, 40年会, 130, 130, (公社)日本薬剤学会, 2025年05月
  日本語
• Dexamethasone dose-dependently attenuates docetaxel-induced peripheral neuropathy in breast cancer treatment.
  Ryota Kanno; Yoshitaka Saito; Yoh Takekuma; Masato Takahashi; Tomohiro Oshino; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 5, 360, 360, 2025年04月07日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Peripheral neuropathy is one of the most problematic adverse effects of docetaxel. We previously reported that dexamethasone (DEX) prevents taxane-associated acute pain syndrome (T-APS) in a dose-dependent manner, which might be a partial manifestation of chemotherapy-induced peripheral neuropathy (CIPN), in breast cancer treatment. Therefore, this study examined the dose-dependent prophylactic efficacy of DEX against CIPN. METHODS: Female patients with breast cancer receiving docetaxel-containing treatments (75 mg/m2) were divided into two groups according to DEX dosage on days 2-4; an 8 mg group (n = 56) and a 4 mg group (n = 28) and retrospectively evaluated. The primary endpoint in this study was defined as the development of grade ≥ 2 CIPN during 4 cycles of the treatment. RESULTS: The incidence of grade ≥ 2 CIPN was 32.1% in the 4 mg group and 10.7% in the 8 mg group and was significantly lower in the 8 mg group (P = 0.03). The incidence of all-grade CIPN was lower in the 8 mg group than in the control group, although the difference was not statistically significant (P = 0.06). Onset time of all-grade and grade ≥ 2 CIPN in the 8 mg group was significantly delayed compared to that in the 4 mg group (P = 0.003 and 0.01, respectively). Additionally, 8 mg/day of DEX was identified as a preventive factor for all-grade CIPN, although the evaluation of grade ≥ 2 symptoms was not possible. CONCLUSION: Our study found that DEX attenuated docetaxel-induced CIPN in a dose-dependent manner during real-world breast cancer treatment. Further studies are needed to develop better CIPN management strategies.
• グラム陽性球菌による骨・関節感染症に対するリネゾリドの第一選択薬としての有効性調査
  新沼 悠介; 石黒 信久; 鏡 圭介; 菅原 満; 武隈 洋
  日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集, 99回・73回, O, 007, 日本感染症学会・日本化学療法学会, 2025年04月
  日本語
• Evaluation of nausea induced by trifluridine/tipiracil in metastatic colorectal cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Journal of chemotherapy (Florence, Italy), 1, 8, 2025年03月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, Trifluridine/tipiracil (FTD/TPI) frequently induces chemotherapy-induced nausea and vomiting (CINV). As evidence of factors associated with CINV in oral chemotherapeutic agents is limited, we aimed to assess factors for nausea development in a real-world FTD/TPI-containing treatment for metastatic colorectal cancer (mCRC). Patients with mCRC receiving FTD/TPI with or without bevacizumab (n = 104) were retrospectively evaluated. Nausea occurred in 40.4% of the patients, and the severity was grade 1 for 23.1%, grade 2 for 15.4%, and grade 3 for 1.9%. Multivariable logistic regression analysis suggested that female sex (adjusted odds ratio 2.74, 95% confidence interval 1.02-7.33, p = 0.045) and concomitant bevacizumab (2.68, 1.13-6.37, p = 0.03) were independent risk factors for all-grade nausea during the first cycle as a primary endpoint. Particularly, among patients with FTD/TPI monotherapy, females significantly exhibited nausea compared to males. Our study revealed that concomitant bevacizumab and female sex are independent risk factors for nausea in FTD/TPI-containing treatment for mCRC.
• Identification of risk factors related to problematic peripheral neuropathy development in gemcitabine and nab-paclitaxel treatment for pancreatic cancer.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 4, 263, 263, 2025年03月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients treated with gemcitabine (GEM) and nanoparticle albumin-bound paclitaxel (nab-PTX) for pancreatic cancer, negatively impacting their quality of life. This study aimed to identify risk factors for significant CIPN development in a real-world setting of GEM + nab-PTX treatment to inform effective management strategies. METHODS: Patients with unresectable pancreatic cancer who received GEM + nab-PTX (n = 140) were retrospectively assessed. The primary endpoint was to identify the risk factor(s) associated with the development of problematic grade ≥ 2 CIPN within six months of treatment initiation. We also evaluated factors associated with all-grade CIPN and compared CIPN incidence across specific patient groups. RESULTS: The incidence of grade ≥ 2 CIPN was 35.0%, with 63.6% of patients experiencing symptoms of any grade. Multivariate Cox proportional hazard regression analysis identified baseline preexisting neuropathy as an independent risk factor for developing grade ≥ 2 CIPN (adjusted hazard ratio 4.03, 95% confidence interval 1.82-8.96, P = 0.0006). Conversely, dose modification of nab-PTX at or within 4 weeks of treatment initiation emerged as a protective factor (0.45, 0.22-0.91, P = 0.03). Additionally, the cumulative incidence of grade ≥ 2 CIPN was significantly lower and delayed in patients who underwent dose modification within 4 weeks compared to those who did not in the population with preexisting neuropathy (P = 0.01). CONCLUSION: Baseline preexisting neuropathy significantly increases the risk, while early dose modification of nab-PTX serves as a protective factor against developing grade ≥ 2 CIPN in patients receiving GEM + nab-PTX treatment for pancreatic cancer.
• Validity and Utility of a Risk Prediction Model for Wound Infection After Lower Third Molar Surgery
  Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Keisuke Okamoto; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
  Oral Diseases, 31, 6, 1922, 1931, Wiley, 2025年01月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, ABSTRACT
  
  Objectives
  
  To externally validate a clinical prediction model for surgical site infection (SSI) after lower third molar (L3M) surgery and evaluate its clinical usefulness.
  
  Methods
  
  We conducted a retrospective cohort study of patients who underwent L3M surgery at Hokkaido University Hospital. The study was designed to evaluate the historical and methodological transportability. Clinical usefulness was evaluated using decision curve analysis on the data of the non‐antibiotic‐treated patients.
  
  Results
  
  We obtained 2543 validation cohorts from April 2020 to March 2023, and 640 non‐antibiotic cohorts from July 2010 to September 2023. The incidences of SSI after L3M surgery were 5.3% (135/2543) and 7.7% (49/640) in the validation and non‐antibiotic cohorts, respectively. The discrimination ability of the prediction model was acceptable for the external validation cohort (c‐statistic: 0.67; 95% CI: 0.62–0.71) and adequate for the non‐antibiotic cohort (c‐statistic: 0.72; 95% CI: 0.63–0.79). In both cohorts, the model showed excellent calibration between the observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.
  
  Conclusion
  
  A simple risk prediction model for SSI after L3M surgery demonstrated clinical transportability and usefulness. This model may help surgeons/clinicians determine the appropriateness of prophylactic antibiotics administration for patients in L3M surgery.
• Relationship Between Anthracycline-cyclophosphamide Regimens and Docetaxel Monotherapy in Oral Mucositis Development.
  Yoshitaka Saito; Tatsuhiko Sakamoto; Yoh Takekuma; Masato Takahashi; Tomohiro Oshino; Mitsuru Sugawara
  In vivo (Athens, Greece), 39, 4, 2259, 2266, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND/AIM: We have previously reported that patients experiencing oral mucositis (OM) during anthracycline-cyclophosphamide treatment develop symptoms following subsequent docetaxel-containing chemotherapy for perioperative breast cancer therapy. However, the concomitant use of pertuzumab and trastuzumab with docetaxel has also been suggested as a significant risk factor for OM. This study aimed to further evaluate the direct relationship of OM with anthracycline-cyclophosphamide treatment and docetaxel monotherapy. PATIENTS AND METHODS: Patients with breast cancer who underwent anthracycline-cyclophosphamide treatment followed by docetaxel monotherapy as perioperative therapy (n=63) were divided into control and OM-experience groups based on the absence or presence of OM development during prior anthracycline-cyclophosphamide treatment, and retrospectively evaluated. The primary endpoint was the comparison of all-grade OM incidence in the first docetaxel cycle between the two groups. The incidence of OM and dysgeusia was also assessed across all treatment cycles. RESULTS: The incidence of all-grade OM was 42.9% in the OM-experience group and 9.5% in the control group during the first cycle (p=0.006) and 47.6% and 11.9% across all treatment cycles (p=0.004), thereby achieving the primary endpoint. In contrast, the incidence of grade ≥2 OM in both settings was higher in the OM-experience group than in the control group, although the difference was not statistically significant (14.3% vs. 2.4%, p=0.10 for both settings). Moreover, the incidence of dysgeusia did not differ between the two groups. CONCLUSION: Patients exhibiting OM during prior anthracycline-cyclophosphamide treatment were significantly more likely to develop symptoms during subsequent docetaxel monotherapy for perioperative breast cancer therapy.
• Evaluation of Transport Activity Using Mouse Jejunal Epithelial Cell Monolayer Culture System.
  Yoshiki Sasagawa; Riho Kamishima; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Yoh Takekuma; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 48, 8, 1199, 1206, 2025年, ［国内誌］
  英語, 研究論文（学術雑誌）
• Severe Hypomagnesemia in a Patient Treated Using Carboplatin Co-Administered with Vonoprazan.
  Osamu Taniguchi; Yoshitaka Saito; Yuka Yamaguchi; Midori Sakai; Yasuyuki Ikezawa; Jun Sakakibara-Konishi; Mina Eguchi; Yoh Takekuma; Mitsuru Sugawara
  Case reports in oncology, 18, 1, 151, 158, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: We describe a case of severe hypomagnesemia that occurred during treatment with carboplatin (CBDCA) and nanoparticle albumin-bound paclitaxel (nab-PTX) for lung adenocarcinoma when co-administered with vonoprazan. CASE PRESENTATION: A man in his 70s was diagnosed with stage IIIA lung adenocarcinoma and received CBDCA and nab-PTX as the first-line treatment. The patient had been taking omeprazole 10 mg once daily (for >3 years) for gastroesophageal reflux disease, but it was switched to lansoprazole 15 mg because of hospital's adopted medication. During the first treatment cycle, his serum creatinine levels increased from 1.0 to 1.5 mg/dL, suggesting CBDCA-associated renal impairment. Because of gastric discomfort on day 15 of the second cycle, lansoprazole was switched to vonoprazan 10 mg once daily. On day 23 of the second cycle, he developed torsades de pointes and was hospitalized; severe hypomagnesemia (0.4 mg/dL) was detected to be causing the symptoms. Discontinuation of vonoprazan and a single intravenous infusion of 60 mEq magnesium sulfate raised serum magnesium levels to 3.7 mg/dL, and the arrhythmia disappeared. Mild hypomagnesemia (1.4 mg/dL) reappeared 5 days later, and an additional intravenous infusion of 20 mEq magnesium sulfate with subsequent oral magnesium oxide (1,980 mg/day) resolved the symptoms. CBDCA was discontinued and nab-PTX monotherapy was continued. Vonoprazan was resumed owing to gastric discomfort relapse; however, grade ≥2 hypomagnesemia did not reappear later. CONCLUSIONS: This case highlights the risk of severe hypomagnesemia in patients with CBDCA and vonoprazan co-administration; therefore, regular monitoring of serum magnesium levels during the treatment is crucial.
• Actual Use of Budesonide Enteric-Coated Capsules for Crohn's Disease in Japan: Analysis of Health Insurance Big Data.
  Keiji Yagisawa; Atsuhito Kubota; Shungo Imai; Shunsuke Nashimoto; Yuki Sato; Hitoshi Kashiwagi; Atsuo Maemoto; Mitsuru Sugawara; Yoh Takekuma
  Biological & pharmaceutical bulletin, 48, 1, 33, 38, 2025年, ［国内誌］
  英語, 研究論文（学術雑誌）, Using a large health insurance database in Japan, we examined the real-world usage of budesonide enteric-coated capsules (BUD) in treating Crohn's disease. We analyzed data from the Japan Medical Data Center claims database for Crohn's disease patients prescribed BUD from April 2016 to March 2021, focusing on prescription status, adverse events (AEs), monitoring tests, and concomitant medications over 2 years following BUD initiation. Patients were categorized into two groups based on BUD usage duration: ≤1 year and >1 year. Of the 7364 registered patients, 1049 (14.2%) were prescribed BUD. Among the 562 followed for 2 years, 505 (89.9%) used BUD for ≤1 year and 57 (10.1%) for >1 year. Over 70% of the patients used at least one biologic, and more than 20% used at least two. The proportions of new thiopurine initiation were 22 and 9% in the ≤1-year and >1-year groups, respectively (p = 0.0181). We did not identify any obvious increase in AEs from long-term BUD use within the confines of our study design. However, regardless of prescription duration, over half of the patients lacked hepatitis B virus screening, glycated hemoglobin measurement, adrenal function quantification, or bone densitometry. Usage of strong CYP3A4 inhibitors was more frequent among patients in the BUD >1-year group. This study revealed that numerous Japanese patients received long-term BUD prescriptions. Although no apparent increase in AEs from long-term BUD was detected, we identified inadequate monitoring of AEs and drug interactions, as well as insufficient use of steroid-sparing agents.
• Impact of Eye Contact on Communication during Online Medication Counseling: An Analysis Using the Roter Interaction Analysis System.
  Ayako Mori; Izumi Kato; Katsuya Narumi; Yoh Takekuma; Shuhei Ishikawa; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Masaki Kobayashi
  Biological & pharmaceutical bulletin, 48, 1, 17, 22, 2025年, ［国内誌］
  英語, 研究論文（学術雑誌）, We have previously used the Roter Interaction Analysis System (RIAS) to analyze differences between online and face-to-face medication counseling. In our previous research, students have commented that the built-in camera on their laptops makes it difficult to make eye contact and communicate effectively. Furthermore, there is a lack of research on the impact of eye contact in online medical communication. Therefore, this study aimed to investigate the effects of eye contact on online medication counseling. Two simulated patients (SPs) and 10 pharmacy students acting as pharmacists were enrolled in this clinical study (ID:2022-001). Participants were divided into 2 groups: one using cameras designed to naturally align eye contact and another using standard device cameras. The dialogues were segmented into meaningful minimal units (utterances), categorized using RIAS according to their nature, and analyzed. Scenarios with aligned eye contact significantly increased the total number of SP utterances and the occurrence and proportion of "Check" utterances by students, confirming their understanding. The increase in the total utterance count of SPs was associated with a corresponding increase in the number of "Agree" utterances indicating agreement and understanding. Thus, eye contact enhances the clarity of patient responses and proactively confirms patient understanding, thereby mitigating the difficulty of assessing comprehension and conducting bidirectional communication online. This study's findings quantitatively suggested that eye contact in online medication counseling enhances proactive engagement in communication for pharmacy students and SPs.
• Comparison of busulfan pharmacokinetics between four-times-daily and once-daily administration in pediatric patients: a preliminary prospective observational trial
  Atsushi Yamaguchi; Shinsuke Hirabayashi; Kazuko Niki; Keisuke Kagami; Yukayo Terashita; Yuko Cho; Atsushi Manabe; Mitsuru Sugawara; Yoh Takekuma
  International Journal of Hematology, 121, 2, 244, 251, Springer Science and Business Media LLC, 2024年12月03日, ［国内誌］
  英語, 研究論文（学術雑誌）, Therapeutic drug monitoring (TDM) of busulfan (BU) is useful for achieving the target area under the curve (AUC) because its effective plasma-concentration range is narrow. This preliminary observational study evaluated the pharmacokinetic (PK) parameters of BU administered four times daily or once daily to pediatric patients. The plasma concentrations were measured at both the test dose and first dose, and the doses on day 1 and days 2-4 were determined based on each TDM. A comparison of PK parameters between four-times-daily and once-daily administration was performed for both the test dose and first dose of BU. Of the 11 patients, five received four-times-daily BU and six received once-daily BU. The Vd for once-daily administration was higher than that for four-times-daily administration for the first dose but not for the test dose. The ratio of actual AUC for the first dose to estimated AUC guided by the test dose was lower with once-daily administration than with four-times-daily administration. These results indicate that the PK parameters of BU administered once daily are challenging to predict based on the TDM of the test dose. TDM should be considered on day 1 to achieve the target AUC, especially with once-daily administration.
• Validated UPLC-MS/MS method for quantification of melatonin receptor agonists and dual orexin receptor antagonists in human plasma and breast milk: Application to quantify suvorexant and lemborexant in clinical samples
  Hina Ishikawa; Ayako Furugen; Ayako Nishimura; Takeshi Umazume; Shuhei Ishikawa; Ryoichi Aoyagi; Katsuya Narumi; Keisuke Okamoto; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
  Journal of Pharmaceutical and Biomedical Analysis, 251, 116432, 116432, Elsevier BV, 2024年12月
  研究論文（学術雑誌）
• Impact of baseline renal impairment on severe neutropenia development in pemetrexed and carboplatin thoracic cancer treatment.
  Yoshitaka Saito; Osamu Taniguchi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 32, 12, 829, 829, 2024年11月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Carboplatin (CBDCA) plus pemetrexed (PEM) is a commonly-used thoracic cancer treatment. As both CBDCA and PEM are excreted via the kidneys, renal impairment (RI) can lead to severe neutropenia, the most typical adverse event in the treatment. We aimed to determine the impact of baseline RI on the development of severe neutropenia following real-world CBDCA + PEM-containing treatments. METHODS: Patients with thoracic cancer receiving CBDCA + PEM-containing treatments (n = 155) were divided into a control group (baseline creatinine clearance [CCr] ≥ 60 mL/min) and an RI group (baseline CCr < 60 mL/min) and retrospectively evaluated. The primary endpoint was the incidence of severe neutropenia during the first cycle. We also assessed factors associated with the development of severe neutropenia. RESULTS: Severe neutropenia during the first cycle was confirmed in 41.2% of the patients in the RI group, which was significantly higher than that in the control group (20.7%, P = 0.02). Additionally, severe neutropenia during all evaluation periods was also more prevalent in the RI group compared to the control group (47.1% vs. 24.8%, P = 0.02). In contrast, the incidence of severe thrombocytopenia was not different. Multivariate logistic regression analyses identified RI as a risk factor for severe neutropenia (adjusted odds ratio 2.71; 95% confidence interval 1.18-6.21, P = 0.02 for the first cycle; 2.62, 1.17-5.84, P = 0.02 for all evaluation periods). CONCLUSION: Our study revealed that patients with baseline RI exhibited severe neutropenia after CBDCA + PEM-containing treatments.
• Effects of famotidine use during pregnancy: an observational cohort study.
  Ayako Nishimura; Ayako Furugen; Masaki Kobayashi; Yoh Takekuma; Naho Yakuwa; Mikako Goto; Masahiro Hayashi; Atsuko Murashima; Mitsuru Sugawara
  Journal of pharmaceutical health care and sciences, 10, 1, 70, 70, 2024年11月08日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Famotidine, a histamine2-receptor antagonist (H2Ras), is widely used to treat and prevent gastrointestinal symptoms during pregnancy. Although several studies have reported the use of H2Ras during pregnancy, limited data on famotidine were included in these reports. Therefore, we analyzed pregnancy outcome data to evaluate the effects of famotidine use during pregnancy on the fetus. METHODS: Pregnancy outcome data were used for females enrolled in two Japanese facilities that provided counseling on drug use during pregnancy between April 1988 and December 2017. For the primary endpoint, the incidence of congenital malformations was calculated from the data of live birth to pregnant women who took famotidine (n = 330) or drugs considered to exert no teratogenic risk (control, n = 1,407) during the first trimester of pregnancy. Considering secondary endpoints, the incidence of obstetric outcomes, including preterm delivery, was calculated from data on the use of famotidine (n = 347) and controls (n = 1,476) during the entire pregnancy. The crude odds ratios (cORs) for the incidence of congenital malformations were calculated using univariate logistic regression analysis, with the control group used as the reference. Adjusted ORs (aORs) were calculated using multivariate logistic regression analysis adjusted for various other factors. RESULTS: The incidences of congenital malformations in the famotidine and control groups were 3.9% and 2.8%, respectively. There was no significant difference between the famotidine and control groups (cOR: 1.40 [95% CI:0.68-2.71], aOR: 1.06 [95% CI:0.51-2.16]). Conversely, the preterm delivery rates were 8.1% and 3.8% in the famotidine and control groups, respectively, indicating a significant difference (cOR: 2.00 [95% CI:1.20-3.27]). However, the multivariate analysis eliminated famotidine use as a confounding factor. CONCLUSIONS: This observational cohort study revealed that exposure to famotidine during the first trimester of pregnancy was not associated with an increased risk of congenital malformations in infants. Although a higher rate of preterm delivery was detected in famotidine users when compared with controls, this could be attributed to confounding factors, such as complications.
• Development and validation of the prediction score for augmented renal clearance in critically Ill Japanese adults.
  Ryusei Mikami; Shungo Imai; Mineji Hayakawa; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  Journal of pharmaceutical health care and sciences, 10, 1, 69, 69, 2024年11月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Augmented renal clearance (ARC) decreases the therapeutic concentration of drugs excreted by the kidneys in critically ill patients. Several ARC prediction models have been developed and validated; however, their usefulness in Japan has not been comprehensively investigated. Thus, we developed a unique ARC prediction model for a Japanese mixed intensive care unit (ICU) population and compared it with existing models. METHODS: This retrospective study enrolled a mixed ICU population in Japan from January 2019 and June 2022. The primary outcome was the development and validation of a model to predict ARC onset based on baseline information at ICU admission. Patients admitted until May 2021 were included in the training set, and external validation was performed on patients admitted thereafter. A multivariate logistic regression model was used to develop an integer-based predictive scoring system for ARC. The new model (the JPNARC score) was externally validated along with the ARC and Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scores. RESULTS: A total of 2,592 critically ill patients were enrolled initially, with 651 patients finally included after excluding 1,941 patients. The training and validation datasets comprised 456 and 195 patients, respectively. Multivariate analysis was performed to develop the JPNARC score, which incorporated age, sex, serum creatinine, and diagnosis upon ICU admission (trauma or central nervous system disease). The JPNARC score had a larger area under the receiver operating characteristic curve than the ARC and ARCTIC scores in the validation dataset (0.832, 0.633, and 0.740, respectively). CONCLUSIONS: An integer-based scoring system was developed to predict ARC onset in a critically ill Japanese population and showed high predictive performance. New models designed to predict the often-unrecognized ARC phenomenon may aid in the decision-making process for upward drug dosage modifications, especially in resource- and labor-limited settings.
• Impact of renal impairment on early development of severe neutropenia with trifluridine/tipiracil treatment for metastatic colorectal cancer.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Scientific reports, 14, 1, 26990, 26990, 2024年11月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, Trifluridine/tipiracil (FTD/TPI) with or without bevacizumab is an effective treatment for metastatic colorectal cancer (mCRC). As this agent is mainly excreted via the kidney, we aimed to evaluate the impact of renal impairment (RI) on the early development of severe neutropenia, a dose-limiting toxicity and whose development reflects better treatment outcomes, in patients with mCRC treated with FTD/TPI. Patients with mCRC receiving FTD/TPI ± bevacizumab (n = 100) were divided into the RI group (creatinine clearance [CCr] < 90 mL/min) or control group (CCr ≥ 90 mL/min), and retrospectively evaluated. Severe neutropenia during the first two cycles occurred in 57.6% and 34.2% of patients in the RI and control groups, respectively, which was significantly different (P = 0.03) and met our primary endpoint. Furthermore, the incidence during the first cycle also differed significantly (52.5% in the RI group and 17.1% in the control group, P = 0.0004). Multivariate logistic regression analysis suggested that baseline RI and neutropenia were significant risk factors for early severe neutropenia (adjusted odds ratio and 95% confidence interval: 3.07, 1.24-7.59, P = 0.02 for RI, and 9.76, 1.08-88.11, P = 0.04 for neutropenia). In conclusion, our study suggested that patients with RI can exhibit early severe neutropenia during real-world FTD/TPI treatment for mCRC.
• Reply to Accurate Risk Prediction Model for Surgical Site Infection After Lower Third Molar Surgery.
  Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
  Oral diseases, 2024年11月03日, ［国際誌］
  英語
• 簡易懸濁法でドラビリンとドルテグラビルを投与後に血漿中薬物濃度を測定した一例
  田澤 佑基; 松川 敏大; 新井 崇之; 遠藤 知之; 武隈 洋; 菅原 満
  日本エイズ学会誌, 26, 4, 402, 402, (一社)日本エイズ学会, 2024年11月
  日本語
• 持続性注射薬カボテグラビル+リルピビリン(CAB+RPV)使用患者の臨床的特徴
  新井 崇之; 田澤 佑基; 遠藤 知之; 武隈 洋; 菅原 満
  日本エイズ学会誌, 26, 4, 417, 417, (一社)日本エイズ学会, 2024年11月
  日本語
• トラブルシューティングに効果的な電子マニュアルの作成・運用
  小柳 遼; 川岸 亨; 水口 貴史; 山崎 浩二郎; 武隈 洋; 菅原 満
  北海道病院薬剤師会誌, 107, 7, 9, (一社)北海道病院薬剤師会, 2024年11月
  日本語
• Effect of baseline anemia on the efficacy of docetaxel and ramucirumab for advanced non-small cell lung cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  BMC cancer, 24, 1, 1301, 1301, 2024年10月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Docetaxel (DOC) and ramucirumab (RAM) is one of the most effective regimens for advanced non-small cell lung cancer (NSCLC) treatment. In our previous study, baseline anemia was identified as a preventive factor against the development of severe adverse effects during the first treatment cycle. It was hypothesized that anemia directly promotes tumor angiogenesis, leading to the elevation of RAM efficacy with increased DOC delivery to tumors, while reducing DOC delivery to other organs, potentially mitigating severe adverse effects. If this hypothesis is correct, patients with baseline anemia may have better clinical outcomes than those with normal hemoglobin levels. In this study, we aimed to investigate the effect of baseline anemia on the efficacy of DOC + RAM in treating advanced NSCLC in a real-word setting. METHODS: Patients with advanced NSCLC receiving DOC + RAM (n = 72) were retrospectively assessed. They were categorized into a control group with normal baseline hemoglobin levels and an anemia group with baseline anemia. The primary endpoint was progression-free survival (PFS) evaluation. RESULTS: Patients in the anemia group had a significantly shorter PFS than that of patients in the control group (median PFS: 3.2 and 6.2 months; 95% confidence interval [CI]: 2.2-4.8 and 4.3-9.9 months, respectively;P = 0.008). In addition, the disease control rate in the anemia group was 65.8%, which was significantly lower than that in the control group (93.6%; P = 0.007). Overall survival tended to be shorter in patients with anemia than in controls, although the difference was not statistically significant (P = 0.07). Multivariate Cox hazard analysis suggested that baseline anemia was a singular risk factor for poor PFS (adjusted hazard ratio 1.84, 95% CI 1.08-3.13; P = 0.02). The incidence of severe adverse effects did not differ between the two groups. CONCLUSIONS: This study suggests that the PFS of patients with anemia treated with DOC + RAM for advanced NSCLC is shorter than that of those without the symptoms.
• Clinical research for saliva-based therapeutic drug monitoring of linezolid.
  Yuki Inoue; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Tsutomu Endo; Masahiko Takahata; Miki Komatsu; Mitsuru Sugawara; Yoh Takekuma
  British journal of clinical pharmacology, 2024年10月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, AIMS: Linezolid is primarily used to treat of methicillin-resistant Staphylococcus aureus and multidrug-resistant tuberculosis infections. Thrombocytopenia due to linezolid usage is a concern, and therapeutic drug monitoring has been reported to be effective in its prevention. Plasma concentrations provide valuable information for treatment decisions; however, collecting plasma samples can be burdensome for both patients and healthcare providers. Therefore, there is interest in saliva as an alternative for monitoring, considering its potential to replace plasma samples. METHODS: Patients hospitalized at Hokkaido University Hospital and Hokkaido Spinal Cord Injury Center between April 2022 and July 2024, who received oral or intravenous linezolid treatment, were enrolled. The concentrations of linezolid were simultaneously measured in plasma and saliva samples. We determined the concentration profiles of linezolid in the saliva and examined the correlation between saliva and plasma linezolid concentrations. RESULTS: Eighteen patients receiving linezolid were enrolled. The average of saliva/plasma (S/P) concentration ratios of linezolid were 1.018. A strong correlation was found between the salivary and plasma concentrations of linezolid (R = .833, P < .001). Notably, in patients receiving intravenous administration of linezolid, the correlation was even more pronounced (R = .885, P < .001). Additionally, when focusing on the S/P ratio of the trough concentrations in the morning and at night, the S/P ratios at night were much closer to 1.0. CONCLUSION: The concentrations of linezolid in plasma and saliva were similar, indicating their potential applicability in clinical settings. The monitoring of linezolid concentrations in saliva has been shown to be particularly suitable for patients receiving intravenous administration.
• Exploring the impact of baseline platelet count on linezolid-induced thrombocytopenia: a retrospective single-center observation study.
  Yuki Inoue; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  International journal of clinical pharmacy, 2024年10月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Patients treated with linezolid (LZD) frequently develop thrombocytopenia, and previous studies have identified the risk factors for this condition. However, the relationship between the development of LZD-induced thrombocytopenia and baseline platelet count has varied according to different reports. AIM: To explore the relationship between platelet count and the development of LZD-induced thrombocytopenia. METHOD: Patients who underwent LZD at Hokkaido University Hospital in Japan from September 2008 to March 2023 were included. We collected data on patient characteristics and platelet counts at baseline and during LZD therapy from the electronic medical records. Thrombocytopenia was defined as a decrease in platelet count by 30% or more from baseline, or a platelet level < 100,000/µL. RESULTS: Two hundred and ninety-five patients who received LZD were included in this study, of whom 34.9% developed thrombocytopenia. In the early days of LZD treatment, the thrombocytopenia group showed a nearly 5% decrease in platelet count, while the non-thrombocytopenia group exhibited an increase of over 5%. Additionally, focusing on early onset thrombocytopenia (within 5 days), a baseline platelet count of < 150,000/µL was identified as a risk factor for early thrombocytopenia. Conversely, it was also observed that 24.7% of patients with a baseline platelet count ≥ 150,000/µL still developed early thrombocytopenia. CONCLUSION: Our findings suggest that while a baseline platelet count of < 150,000/µL is a risk factor for the early onset of thrombocytopenia, vigilant monitoring of platelet counts by clinical pharmacists in the early stages of LZD treatment is essential, regardless of baseline platelet levels.
• The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci.
  Yusuke Niinuma; Keisuke Kagami; Mitsuru Sugawara; Yoh Takekuma
  Journal of chemotherapy (Florence, Italy), 1, 8, 2024年08月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, The area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio was used as an indicator of the clinical efficacy of vancomycin. However, the target AUC/MIC has not been set for methicillin-resistant coagulase-negative staphylococci (MR-CNS), and the effectiveness of vancomycin in strains with high MIC is unknown. Therefore, we aimed to investigate the relationship between the vancomycin MIC and therapeutic efficacy in patients with MR-CNS bacteremia. The primary outcome was the difference in treatment failure rate when the MR-CNS vancomycin MIC was 1 or 2 µg/mL. The treatment failure rate did not significantly differ between the two groups (MIC 1 vs. MIC 2: 27.0% vs. 31.0%; p = 0.779). As a result of multivariate analysis, AUC/MIC0-24 h ≤230 was extracted as risk factor for treatment failure, suggesting the importance of a sufficient initial loading dose and early blood concentration monitoring to increase AUC/MIC0-24 h for successful treatment.
• Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.
  Yoshitaka Saito; Yoh Takekuma; Masato Takahashi; Tomohiro Oshino; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 32, 8, 513, 513, 2024年07月13日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.
• オレキシン受容体拮抗薬のUPLC/MS/MS定量法構築とヒト乳汁移行性評価への応用
  石川 陽菜; 古堅 彩子; 西村 あや子; 馬詰 武; 青柳 亮一; 石川 修平; 鳴海 克哉; 岡本 敬介; 武隈 洋; 菅原 満; 小林 正紀
  TDM研究, 41, 2, 149, 149, (一社)日本TDM学会, 2024年07月
  日本語
• 小児造血幹細胞移植におけるブスルファンの1日4回投与法と1日1回投与法による薬物動態パラメータの比較
  山口 敦史; 平林 真介; 仁木 加寿子; 鏡 圭介; 寺下 友佳代; 長 祐子; 真部 淳; 菅原 満; 武隈 洋
  TDM研究, 41, 2, 155, 155, (一社)日本TDM学会, 2024年07月
  日本語
• メチシリン耐性コアグラーゼ陰性ブドウ球菌におけるバンコマイシンMICと治療効果の関連性
  新沼 悠介; 鏡 圭介; 武隈 洋; 菅原 満
  TDM研究, 41, 2, 172, 172, (一社)日本TDM学会, 2024年07月
  日本語
• Evaluation of the impact of systemic dexamethasone dosage on docetaxel-induced hand-foot syndrome in patients with breast cancer.
  Yoshitaka Saito; Yoh Takekuma; Masato Takahashi; Tomohiro Oshino; Mitsuru Sugawara
  Scientific reports, 14, 1, 14083, 14083, 2024年06月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m2)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2-4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14-0.86, P = 0.02 for all cycles; 0.26, 0.11-0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.
• Dolutegravir/lamivudineへの薬剤変更における薬剤師介入の効果
  田澤 佑基; 遠藤 知之; 武隈 洋; 菅原 満
  日本エイズ学会誌, 26, 2, 77, 84, (一社)日本エイズ学会, 2024年05月
  日本語
• ナノリポソーマルイリノテカンとレボホリナートの並列投与における有効性、安全性の評価
  坂本 達彦; 齋藤 佳敬; 渡辺 拓也; 内山 数貴; 武隈 洋; 小松 嘉人; 菅原 満
  日本臨床腫瘍薬学会雑誌, 36, 191, 191, (一社)日本臨床腫瘍薬学会, 2024年05月
  日本語
• Immunoregulatory Effects of Elemental Diet and Its Ingredient, Tryptophan, via Activation of the Aryl Hydrocarbon Receptor in Mice
  Atsuhito Kubota; Shungo Imai; Ryoichi Aoyagi; Wataru Murase; Masaru Terasaki; Mitsuru Sugawara; Yoh Takekuma; Hiroyuki Kojima
  International Journal of Molecular Sciences, 25, 6, 3448, 2024年03月19日, ［査読有り］, ［招待有り］
  英語, 研究論文（学術雑誌）
• Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.
  Takuya Watanabe; Yoshitaka Saito; Yoh Takekuma; Yasushi Shimizu; Ichiro Kinoshita; Yoshito Komatsu; Mitsuru Sugawara
  International journal of clinical pharmacology and therapeutics, 2024年03月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. MATERIALS AND METHODS: Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. RESULTS: Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). CONCLUSION: We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.
• Impact of preexisting proteinuria on the development of regorafenib-induced problematic proteinuria in real-world metastatic colorectal cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Scientific reports, 14, 1, 5153, 5153, 2024年03月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1-2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45-9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation.
• Evaluation of Prediabetes in Cisplatin-induced Nephrotoxicity in the Short Hydration Method: A Subgroup Analysis
  YOSHITAKA SAITO; TATSUHIKO SAKAMOTO; MASAKI KOBAYASHI; YOH TAKEKUMA; ISSEI HIGUCHI; KEISUKE OKAMOTO; JUN SAKAKIBARA-KONISHI; YASUSHI SHIMIZU; ICHIRO KINOSHITA; MITSURU SUGAWARA
  In Vivo, 38, 2, 800, 806, Anticancer Research USA Inc., 2024年02月28日
  研究論文（学術雑誌）
• コロナウイルス感染症流行時の病院実習における栄養サポートチーム(NST)実習を遠隔配信で行った場合の教育効果
  巽 道代; 熊谷 聡美; 七戸 俊明; 片山 真育; 武隈 洋; 菅原 満
  薬学教育, 7, 213, 221, (一社)日本薬学教育学会, 2024年01月
  日本語
• 新たなTDM対象抗菌薬の最前線 オキサゾリジノン系抗菌薬のTDM
  武隈 洋; 井上 優希; 菅原 満
  感染症学雑誌, 98, 1, 53, 53, (一社)日本感染症学会, 2024年01月
  日本語
• Association Between Multisystem Immune-related Adverse Events and Progression-free Survivals in PD-1/PD-L1 Inhibitor Monotherapy.
  Atsushi Yamaguchi; Yoshitaka Saito; Keisuke Okamoto; Ayako Furugen; Katsuya Narumi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara; Masaki Kobayashi
  In vivo (Athens, Greece), 38, 6, 2886, 2896, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND/AIM: Immune-related adverse events (irAEs) occur in various organs, and sometimes multiply following treatment with immune checkpoint inhibitors (ICIs). This study aimed to determine the association between the number of irAEs and clinical outcomes. PATIENTS AND METHODS: This was a retrospective study that included patients with lung cancer, melanoma, and head and neck cancer who were treated with anti-programmed cell death (ligand) 1 (PD-1/PD-L1) monotherapy. We evaluated the association between the number of irAEs and progression-free survival (PFS) in the simple Cox regression analysis. To eliminate the immortal-time bias, an additional landmark analysis was performed. RESULTS: In total, 92, 69, and 37 patients were allocated to the no, single, and multisystem irAEs groups, respectively. The multisystem irAEs were associated with better PFS compared to the no irAE group. In contrast, at the 12-week landmark, multisystem irAEs were associated with poor PFS compared to the no irAEs group. Furthermore, the rate of treatment suspension owing to irAEs in the multisystem irAEs group (62.5%) was higher than that in the single irAE group (17.3%) at the 12-week landmark. CONCLUSION: The incidence of multisystem irAEs was associated with improved clinical outcomes in patients with lung cancer, melanoma, and head and neck cancer treated with PD-1/PD-L1 inhibitor monotherapy. However, these results may be influenced by a potential immortal-time bias. When accounting for this bias, the early development of multisystem irAEs within 12 weeks was linked to treatment suspension and poorer clinical outcomes.
• Risk Factor Analysis for Anti-epidermal Growth Factor Receptor Monoclonal Antibody-induced Problematic Skin Toxicities in Patients With Liver Metastatic Colorectal Cancer.
  Yoshitaka Saito; Kazuki Uchiyama; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  In vivo (Athens, Greece), 38, 5, 2390, 2398, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND/AIM: We previously reported that patients with metastatic colorectal cancer (mCRC) and baseline liver metastasis are at a higher risk of developing grade ≥2 overall skin toxicities when treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This study aimed to identify additional factors associated with skin toxicities induced by anti-EGFR treatment in patients with liver metastatic CRC. PATIENTS AND METHODS: Patients with liver metastatic CRC who initially received anti-EGFR monoclonal antibody-containing treatment (n=77) were retrospectively assessed. The primary endpoint was to identify the factor(s) responsible for the development of grade ≥2 overall skin toxicities. Additionally, factors for grade ≥2 rash and paronychia were evaluated. RESULTS: The incidence of grade ≥2 overall skin symptoms, rash, and paronychia was 62.3%, 31.2%, and 28.6%, respectively. Multivariate Cox proportional hazard regression analyses revealed that age <65 years and anemia were independent baseline risk factors for grade ≥2 overall skin toxicities (adjusted hazard ratio 2.09, 95% confidence interval=1.10-3.97, p=0.02 for age; 2.36, 1.20-4.61, p=0.01 for anemia). In contrast, combination prophylaxis using systemic minocycline and corticosteroid ointment was a preventive factor (0.47, 0.25-0.88, p=0.02). Males and age <65 years were baseline risk factors for grade ≥2 rash, and combination prophylaxis was identified as a preventive factor. No factors were identified for paronychia. CONCLUSION: Age <65 years and anemia were identified as independent baseline risk factors. Additionally, combination prophylaxis was found to be a preventive factor against anti-EGFR monoclonal antibody-induced grade ≥2 overall skin toxicities in patients with liver metastatic CRC.
• Evaluation of Efficacy of Adding Aprepitant to Palonosetron and Dexamethasone in Carboplatin and Etoposide Therapy.
  Tatsuhiko Sakamoto; Moeko Kado; Yoshitaka Saito; Kazuki Uchiyama; Ryota Kanno; Osamu Taniguchi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 47, 6, 1189, 1195, 2024年, ［国内誌］
  英語, 研究論文（学術雑誌）, Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
• Platelets Affect the Activity of Amino Acid Transporter SNAT4 in HuH-7 Human Hepatoma Cells.
  Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Shungo Imai; Yoh Takekuma; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 47, 3, 652, 659, 2024年, ［国内誌］
  英語, 研究論文（学術雑誌）, Platelets have been reported to exert diverse actions besides hemostasis and thrombus formation in the body. However, whether platelets affect transporter activity remains to be determined. In this study, we examined the effects of platelets on the activity of amino acid transporter system A, which is known to be changed by various factors, and we clarified the mechanism by which platelets affect system A activity. Among system A subtypes, we found that sodium-coupled neutral amino acid transporter (SNAT) 4 played a central role in the transport activity of system A in HuH-7 human hepatoma cells. Interestingly, platelets showed a biphasic effect on system A activity: activated platelet supernatants (APS) including the granule contents released from platelets downregulated system A activity at lower concentrations and the downregulation was suppressed at higher concentrations. The downregulation was due to a decrease in the affinity of SNAT4 for its substrate and not a decrease in the SNAT4 abundance on the plasma membrane. In addition, APS did not decrease the expression level of SNAT4 mRNA. On the other hand, platelets did not affect system A activity when the platelet suspension was added to HuH-7 cells. These results indicate that platelets indirectly affect the transport activity of system A by releasing bioactive substances but do not directly affect it by binding to HuH-7 cells.
• Decrease in Mycophenolic Acid Plasma Level by Sacubitril/Valsartan in a Lupus Nephritis Patient: A Case Report.
  Shunsuke Nashimoto; Masashi Miyamae; Issei Higuchi; Michihito Kono; Maria Tada; Tatsuya Atsumi; Mitsuru Sugawara; Yoh Takekuma
  Case reports in nephrology and dialysis, 14, 1, 30, 35, 2024年, ［国際誌］
  英語, INTRODUCTION: Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan. CASE PRESENTATION: The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 μg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 μg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 μg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration. CONCLUSION: Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.
• Significantly Delayed Development of Polyarthritis with Active Tenosynovitis after Possible Temporary Neutropenic Immune-Related Adverse Events Caused by Atezolizumab Treatment: A Novel Case Report.
  Yoshitaka Saito; Yoh Takekuma; Hajime Asahina; Ryo Hisada; Mitsuru Sugawara
  Case reports in oncological medicine, 2024, 1566299, 1566299, 2024年, ［国際誌］
  英語, Immune checkpoint inhibitors have drastically improved cancer treatment. However, they may induce immune-related adverse events (irAEs). Here, we report a case of significantly delayed rheumatic irAEs (Rh-irAEs) with prior possible temporary neutropenic irAEs in a patient with atezolizumab-treated non-small-cell lung cancer and its management. A man in his sixties received atezolizumab monotherapy as the sixth-line treatment. He experienced an infusion-related reaction (fever) during the first cycle. On day 22 of cycle 2, grade 4 neutropenia suddenly appeared, but it disappeared on the next day. Cycle 3 was initiated after seven days; the patient did not exhibit any symptoms for approximately 500 days. However, on day 534 (day 1 of cycle 21), the patient complained of pain in the shoulders, back, and wrists. On day 644, the shoulder and back pain worsened with obvious swelling of the fingers. We thus suspended treatment and consulted a rheumatologist. A diagnosis of polyarthritis with active tenosynovitis was made based on joint ultrasound and laboratory tests. Prednisolone 15 mg attenuated the symptoms, allowing suspension of analgesics; however, dose reduction from 15 mg/day was difficult because of symptom flares. Finally, iguratimod 25 mg twice daily was initiated on day 764; prednisolone was reduced to 10 mg without flares, and its dosage was slowly reduced to 5 mg/day. Although irAEs exhibit multisystem features, delayed development of polyarthritis with active tenosynovitis after possible temporary neutropenic irAEs is rare. Thus, irAEs need to be monitored for a long time in patients with suspected irAE development even if it appears transiently.
• Comparison of the incidence of nausea and vomiting between linezolid and vancomycin using claims database: a retrospective cohort study.
  Takezo Tsutsumi; Shungo Imai; Kenji Momo; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Yoh Takekuma
  International journal of clinical pharmacy, 2023年12月29日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Nausea and vomiting during linezolid therapy have been reported as part of safety analyses in clinical trials. We have previously examined the incidence of vomiting during linezolid therapy (18.1%). A previous study conducted at a single hospital showed low external validity. It is necessary to verify whether these results can be reproduced using generalizable data sources. AIM: To evaluate the incidence of nausea and vomiting during linezolid therapy compared with vancomycin using a Japanese claims database. METHOD: Patients administered linezolid or vancomycin were selected from the database between January 2005 and June 2017. The primary endpoint was the comparison of nausea and vomiting between the linezolid and vancomycin groups. We conducted propensity score matching (PSM) to adjust for patient characteristics. To assess risk factors for nausea and vomiting, logistic regression was conducted as the secondary endpoint. We defined nausea and vomiting as the first prescription of antiemetics during linezolid or vancomycin therapy as a surrogate endpoint. RESULTS: In total, 1215 patients were enrolled. After PSM, the number of patients in the linezolid and vancomycin groups was 241. Nausea and vomiting were observed in 11.2% and 5.0% of patients in the linezolid and vancomycin groups, respectively (p < 0.05). Linezolid administration was extracted as a risk factor for nausea and vomiting (odds ratio, 2.09; 95% confidence interval, 1.02-4.30). CONCLUSION: This study clarified the relationship between linezolid and nausea and vomiting using a Japanese claims database. Further studies are required to elucidate the unknown mechanisms of linezolid-induced nausea and vomiting.
• Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis
  Atsushi Yamaguchi; Yoshitaka Saito; Yoh Takekuma; Mitsuru Sugawara
  Supportive Care in Cancer, 32, 1, Springer Science and Business Media LLC, 2023年12月26日
  研究論文（学術雑誌）
• Evaluation of the additional prophylactic effect of topical steroid ointment to systemic minocycline against anti-epidermal growth factor antibody-induced skin toxicities in metastatic colorectal cancer treatment.
  Yoshitaka Saito; Kazuki Uchiyama; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 32, 1, 8, 8, 2023年12月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibodies often cause skin toxicities. Preemptive skin treatments using systemic antibiotics with or without topical steroid are reportedly effective although the most suitable method remains unclear. This study aimed to determine whether combination prophylaxis using systemic minocycline and topical steroid is superior to minocycline alone in a real-world metastatic colorectal cancer (mCRC) treatment. METHODS: Patients with mCRC (n = 87) who received anti-EGFR monoclonal antibodies were retrospectively assessed. The primary objective was to compare the incidence of grade ≥ 2 overall skin toxicities during all treatment periods between the control group receiving prophylactic minocycline 100 mg/day, and the combination prophylaxis group receiving minocycline 100 mg/day + topical steroid. The incidence of each skin symptom was also evaluated. RESULTS: The incidence of grade ≥ 2 overall skin toxicities was 63.6% in the control and 56.9% in the combination groups, with no significant difference (P = 0.63). Similarly, the incidence of grade ≥ 2 dry skin, fissures, paronychia, and pruritus did not significantly differ. In addition, incidence of all-grade skin toxicities was not different. However, the incidence of grade ≥ 2 papulopustular rashes was significantly lower in the combination group (23.1% vs. 50.0%, P = 0.03). Propensity score-matched analysis supported these results. Multivariate logistic regression analysis showed no significant association between combination prophylaxis and grade ≥ 2 overall skin toxicities, but it did show a reduction in grade ≥ 2 papulopustular rashes. CONCLUSION: Adding topical steroids to systemic minocycline did not mitigate grade ≥ 2 overall skin toxicities induced by anti-EGFR antibodies; however, it significantly improved papulopustular rashes.
• Detection of factors related to treatment reduction in docetaxel and ramucirumab for non-small cell lung cancer treatment.
  Yoshitaka Saito; Shinya Tamaki; Daisuke Hirate; Shinya Takada; Kenta Takahashi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Scientific reports, 13, 1, 19457, 19457, 2023年11月09日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12-0.66; P = 0.004 for baseline anemia, 0.18; 0.08-0.42; P < 0.0001 for prophylactic G-CSF administration). The primary cause of the reduction was febrile neutropenia, and the same factors were identified. Our study revealed that patients with baseline anemia and prophylactic G-CSF administration have less risk for treatment reduction in DOC + RAM for NSCLC treatment.
• Risk factor analysis for cisplatin-induced nephrotoxicity with the short hydration method in diabetic patients.
  Yoshitaka Saito; Masaki Kobayashi; Shinya Tamaki; Katsuyuki Nakamura; Daisuke Hirate; Kenta Takahashi; Yoh Takekuma; Jun Sakakibara-Konishi; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Scientific reports, 13, 1, 17126, 17126, 2023年10月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients. Patients with thoracic cancer requiring DM pharmacotherapy, who received CDDP (≥ 60 mg/m2)-containing regimens using the short hydration method (n = 140), were enrolled in this retrospective multicenter observational study. The primary endpoint of the present study was the elucidation of risk factors (patient factors, DM medication influence, and treatment-related factors) associated with CIN development in patients with DM. Cisplatin-induced nephrotoxicity occurred in 22.1% of patients with DM. The median worst variation of serum creatinine levels and creatinine clearance (worst level - baseline level) was 0.16 mg/dL (range: - 0.12-1.41 mg/dL) and - 15.9 mL/min (- 85.5-24.3 mL/min), respectively. Multivariate logistic regression analyses identified female sex as the singular risk factor for CIN development in the DM population (adjusted odds ratio; 2.87, 95% confidence interval; 1.08-7.67, P = 0.04). Diabetes mellitus medication and treatment-related factors did not affect CIN development. In conclusion, our study revealed that female sex is significantly associated with CIN development in patients with DM and thoracic cancer.
• Quantitative analysis of communication changes in online medication counseling -Using the Roter Interaction Analysis System.
  Ayako Mori; Izumi Kato; Katsuya Narumi; Yoh Takekuma; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Masaki Kobayashi
  Research in social & administrative pharmacy : RSAP, 2023年10月04日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Quantitative analysis and objective evaluation of communication play an important role in medical communication education. In the process of developing an online methodology for medication counseling practice, we felt the necessity of conducting a quantitative evaluation to enhance its effectiveness. OBJECTIVES: This study aimed to quantitatively evaluate the communication in each scenario to comprehensively identify the differences between face-to-face and online communication in medication counseling practicum. In addition, we examined how patient satisfaction changes between face-to-face and online interactions. METHODS: Face-to-face and online role-playing were conducted between simulated patients (SPs) and students acting as pharmacists, and their dialogues were videotaped. The utterances in each recorded dialogue were categorized and analyzed by the Roter interaction analysis system (RIAS). The Japanese version of the Medical Interview Satisfaction Scale (MISS-21J) responses of the SPs were analyzed for the patient satisfaction survey. RESULT: The results of the RIAS analysis revealed that the socio-emotional category appeared significantly more frequently in face-to-face communication, with more utterances that were more attuned to the feelings of the other person and more considerate of his or her feelings. The ratio of the number of utterances between students and SPs suggested that the communication was more interactive. CONCLUSION: Based on the respective communication tendencies may have led to higher satisfaction in face-to-face than in online patient satisfaction surveys, less anxiety about illness and medications, and easier trusting relationships. Since it is difficult to grasp the mood of the other party and to open up to them due to the lack of nonverbal information in online dialogue, it is necessary to be more conscious of conversations that capture the feelings of patients in online medication counseling.
• Development of a risk prediction model for surgical site infection after lower third molar surgery.
  Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
  Oral diseases, 2023年09月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. METHODS: We conducted a nested case-control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. RESULTS: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3-10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance-statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. CONCLUSIONS: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible.
• Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study.
  Keisuke Kagami; Reiko Oyamada; Tsubasa Watanabe; Sho Nakakubo; Takahiro Hayashi; Sumio Iwasaki; Tatsuya Fukumoto; Takayuki Usami; Kasumi Hayasaka; Shinichi Fujisawa; Chiaki Watanabe; Mutsumi Nishida; Takanori Teshima; Yusuke Niinuma; Isao Yokota; Yoh Takekuma; Mitsuru Sugawara; Nobuhisa Ishiguro
  International journal of nursing practice, 29, 5, e13195, 2023年08月24日, ［国際誌］
  英語, 研究論文（学術雑誌）, AIM: The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2. BACKGROUND: The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important. DESIGN: A Retrospective Cohort Study was conducted. METHODS: When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis. RESULTS: Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission. CONCLUSION: If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.
• Risk factor analysis for anti-epidermal growth factor receptor monoclonal antibody-induced skin toxicities in real-world metastatic colorectal cancer treatment.
  Yoshitaka Saito; Kazuki Uchiyama; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 31, 8, 504, 504, 2023年08月02日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their administration induces skin toxicity, markedly reducing patients' quality of life. This study is aimed at identifying the risk factors associated with anti-EGFR monoclonal antibody-induced skin toxicities. METHODS: Patients with mCRC (n = 116) who received anti-EGFR monoclonal antibody treatment were retrospectively evaluated. Primary endpoint was evaluation of the risk factors for grade ≥ 2 overall skin toxicities during all the treatment periods. Furthermore, factors associated with each grade ≥ 2 skin symptoms were assessed. RESULTS: Incidence of total grade ≥ 2 skin toxicity symptoms was 61.2%, and those of grade ≥ 2 rash, dry skin, fissures, and paronychia were 34.5%, 25.9%, 20.7%, and 25.0%, respectively. Multivariate logistic regression analyses revealed that liver metastasis was an independent risk factor for overall grade ≥ 2 skin toxicities (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.22-6.78; P = 0.02) and prophylactic administration of antibiotics as a preventive factor (OR 0.10; 95%CI 0.01-0.91; P = 0.04). For grade ≥ 2 rash, prophylactic use of systemic antibiotics and topical steroid ointment was a preventive factor (OR 0.37; 95%CI 0.16-0.89; P = 0.03). Moreover, liver metastasis (OR 8.37; 95%CI 1.98-35.47; P = 0.004) and prophylactic administration of antibiotics (OR 0.15; 95%CI 0.03-0.76; P = 0.02) were significantly associated with grade ≥ 2 paronychia. CONCLUSION: Liver metastasis was suggested to be a risk factor for the incidence of overall grade ≥ 2 skin toxicities; moreover, preemptive systemic antibiotic administration drastically decreased this risk during all periods of anti-EGFR treatment for mCRC.
• Correlation between antibiotic use and resistance of gram-negative bacteria at a university hospital in Japan from 2013 to 2021: a study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system.
  Keisuke Kagami; Nobuhisa Ishiguro; Sumio Iwasaki; Keisuke Taki; Tatsuya Fukumoto; Kasumi Hayasaka; Reiko Oyamada; Tsubasa Watanabe; Sho Nakakubo; Yusuke Niinuma; Mitsuru Sugawara; Yoh Takekuma
  European journal of hospital pharmacy : science and practice, 2023年07月12日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVES: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures. We aimed to investigate the correlation between antibiotic use and AMR at a university hospital from 2013 to 2021 in a time series analysis using the J-SIPHE system. We also studied this correlation in each ward (inter-ward analysis). METHODS: Data on antibiotic use and resistance rates were collected from the J-SIPHE system, except for the resistance rate in each ward, which was calculated from the source data prepared for this system. RESULTS: Piperacillin/tazobactam use was positively correlated with piperacillin/tazobactam resistance in Escherichia coli and Klebsiella pneumoniae in the inter-ward analysis, and in Pseudomonas aeruginosa in both analyses. Carbapenem use was positively correlated with meropenem resistance in Enterobacter cloacae in the time series analysis and in P. aeruginosa in both analyses, and imipenem/cilastatin resistance in P. aeruginosa in inter-ward analysis. Quinolone use was positively correlated with levofloxacin resistance in E. coli in both analyses, and in K. pneumoniae in inter-ward analysis. CONCLUSIONS: This is the first study to investigate the correlation between antibiotic use and AMR at a single hospital in time series and inter-ward analyses using the J-SIPHE system and data prepared for this system, suggesting that this system may be useful for promoting AMR measures.
• Acid suppressants reduce the therapeutic effect of immune checkpoint inhibitors and increase the risk of acute kidney injury: a meta-analysis
  Keisuke Okamoto; Yoshitaka Saito; Atsushi Yamaguchi; Yoh Takekuma; Mitsuru Sugawara
  International Journal of Clinical Oncology, Springer Science and Business Media LLC, 2023年07月08日, ［査読有り］
  研究論文（学術雑誌）
• Monitoring Salivary Concentrations of Tedizolid and Linezolid Using Rats
  Yuki Inoue; Yuki Sato; Hitoshi Kashiwagi; Shunsuke Nashimoto; Mitsuru Sugawara; Yoh Takekuma
  European Journal of Drug Metabolism and Pharmacokinetics, Springer Science and Business Media LLC, 2023年06月27日, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• Impact of systemic dexamethasone dosage on docetaxel-induced oral mucositis in patients with breast cancer.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Tomohiro Oshino; Mitsuru Sugawara
  Scientific reports, 13, 1, 10169, 10169, 2023年06月22日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Oral mucositis (OM) is a common adverse effect of docetaxel-containing treatment. This study aimed to assess whether dexamethasone (DEX) dose-dependently attenuates docetaxel-induced OM and dysgeusia. We retrospectively analyzed medical records of patients with breast cancer receiving docetaxel-containing regimens at Hokkaido University Hospital between June 2015 and June 2022. The patients were divided into low-dose and high-dose groups (DEX 4 or 8 mg/day on days 2-4, respectively), and incidence of OM and dysgeusia, and risk factor(s) for OM incidence were evaluated. The incidence of all-grade OM in the first cycle was 57.8% in the low-dose group and 19.2% in the high-dose group (P = 0.0002), which met our primary endpoint. The incidence of OM in all treatment cycles was also significantly lowered by DEX-dose increase (P = 0.01). In contrast, the incidence of dysgeusia was similar between the two groups in the first and all cycles (P = 0.50 and P = 0.28, respectively). These results were also confirmed in a propensity score-matched population. Multivariate logistic regression analysis also suggested that lower DEX dosage was a singular risk factor for all-grade OM incidence. In conclusion, our study suggests that DEX dose-dependently reduces the incidence of OM in docetaxel-containing regimens for breast cancer treatment.
• Severe hypertension development significantly improves progression-free survival in regorafenib treatment for metastatic colorectal cancer.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  International journal of clinical oncology, 28, 9, 1183, 1190, 2023年06月15日, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Regorafenib is the first multikinase inhibitor used for metastatic colorectal cancer (mCRC) treatment. Reports regarding other multikinase inhibitors have suggested that the development of hypertension is associated with improved clinical benefits. We aimed to reveal the relationship between the development of severe hypertension and regorafenib efficacy in an mCRC real-world setting. METHODS: Patients with mCRC (n = 100) who received regorafenib were assessed retrospectively. The primary endpoint was a comparison of progression-free survival (PFS) between patients with and without ≥ grade 3 hypertension. The secondary endpoints were overall survival (OS), disease control rate (DCR), and adverse effects. RESULTS: Patients developing ≥ grade 3 hypertension accounted for 30%, and obtained significantly longer PFS than control patients (median PFS of 53 and 56 days, 95% confidence interval [CI] of 46-144 and 49-63 days, respectively; P = 0.04). In contrast, OS and DCR were not statistically different between the groups (P = 0.13 and P = 0.46, respectively). The incidence and severity of adverse effects were not significantly different, except for hypertension. Treatment interruption was significantly more frequent in patients with hypertension (P = 0.04). Multivariate Cox hazard analysis suggested that the development of ≥ grade 3 severe hypertension was an independent factor for improved PFS (adjusted hazard ratio 0.57, 95% CI 0.35-0.93; P = 0.02). In contrast, baseline hypoalbuminemia was associated with a worse PFS (1.85, 1.14-3.01; P = 0.01). CONCLUSION: We have revealed that patients who develop severe hypertension after regorafenib treatment for mCRC have improved PFS. Management of hypertension is important for effective treatment with less burden; therefore, further evaluation is needed.
• High dose of dexamethasone attenuates docetaxel-induced fluid retention in breast cancer treatment.
  Yoshitaka Saito; Ryota Kanno; Yoh Takekuma; Takashi Takeshita; Tomohiro Oshino; Mitsuru Sugawara
  Scientific reports, 13, 1, 9247, 9247, 2023年06月07日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Docetaxel-induced fluid retention (DIFR) cumulatively occurs and is one of the most troublesome adverse effects. This study aimed to determine whether high dose dexamethasone (DEX) could prevent DIFR during breast cancer treatment. Breast cancer patients receiving docetaxel (75 mg/m2)-containing regimens were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2-4 and retrospectively assessed. Incidence of greater than or equal to grade 2 DIFR was significantly lower in the 8 mg group (13.0%) compared to the 4 mg group (39.6%, P = 0.001). All-grade DIFR was also less in the 8 mg group (P = 0.01). Furthermore, the maximum variation of body weight was significantly lower in the 8 mg group (P = 0.0003). These results were also confirmed in the propensity score-matched population. Additionally, time-related DIFR incidence was also significantly delayed in the 8 mg group (P = 0.0005). Our study revealed that high dose DEX prevents DIFR. Therefore, further studies on its management are required for less onerous chemotherapy provision with better DIFR control.
• Dexamethasone dose-dependently prevents taxane-associated acute pain syndrome in breast cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Tomohiro Oshino; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 31, 6, 372, 372, 2023年06月03日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Taxane-associated acute pain syndrome (T-APS) is one of the most bothersome adverse effects caused by taxanes. We have previously reported the attenuating effect of dexamethasone (DEX) on T-APS and its risk factors under DEX prophylaxis. However, the appropriate DEX dosage administration remains unclear. Therefore, this study aimed to investigate whether DEX dose-dependently prevents T-APS in breast cancer patients. METHODS: We retrospectively evaluated patients with breast cancer who received docetaxel (75 mg/m2)-containing chemotherapy without pegfilgrastim and regular non-steroidal anti-inflammatory drugs. The patients were divided into 4 mg/day and 8 mg/day DEX groups, with each DEX dosage on days 2-4 (n = 68 for each group). Primary endpoint was the comparison of all-grade T-APS incidence between the groups. Propensity score-matching was performed to adjust the baseline factors between the groups, and outcomes in the matched-population were also assessed. RESULTS: The incidence of all-grade T-APS was 72.1% in 4 mg/day group and 48.5% in 8 mg/day group, which was significantly lowered by higher DEX dosage (P = 0.008). The severity of T-APS was also significantly reduced in 8 mg/day group (P = 0.02). These results were confirmed in the propensity score matching. Multivariate logistic analysis showed that higher DEX dosage was an independent T-APS preventive factor, whereas age < 55 years was a risk factor. Moreover, DEX-dosage-associated adverse effects similarly appeared in both groups. CONCLUSION: Our study suggested that DEX dose-dependently prevents T-APS in breast cancer treatment. As understanding of the nature of T-APS and its appropriate management can significantly contribute to less onerous chemotherapy provision, further studies are required.
• Therapeutic Drug Monitoring of Oral Voriconazole in an Infant Less than Six Months of Age and Pharmacokinetics Changes Induced by Development of CYP2C19 in the Growth Process: A Novel Case Report
  Atsushi Yamaguchi; Yuki Tazawa; Masashiro Ueki; Masafumi Yamada; Atsushi Manabe; Mitsuru Sugawara; Yoh Takekuma
  YAKUGAKU ZASSHI, 143, 6, 545, 549, Pharmaceutical Society of Japan, 2023年06月01日, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• Efficacy of antacids for cisplatin-induced gastrointestinal symptoms in the treatment of lung cancer.
  Osamu Taniguchi; Yoshitaka Saito; Yoh Takekuma; Hirotoshi Akita; Ichiro Kinoshita; Yasushi Shimizu; Naofumi Shinagawa; Mitsuru Sugawara
  International journal of clinical pharmacology and therapeutics, 61, 6, 246, 254, 2023年03月27日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) and chemotherapy-associated dyspepsia syndrome (CADS) are frequently appearing adverse effects of cisplatin (CDDP)-containing chemotherapy. Antiemetic guidelines suggest that the administration of antacids such as proton pump inhibitors (PPIs) or histamine type-2 receptor antagonists be considered for CADS, although their efficacy for treating these symptoms remains unknown. This study aimed to reveal whether antacids attenuate gastrointestinal symptoms in CDDP-containing chemotherapy. MATERIALS AND METHODS: In total, 138 patients with lung cancer who received ≥ 75 mg/m2 CDDP-containing regimens were enrolled in this retrospective study. Patients were divided into an antacid group including patients administered PPIs or vonoprazan during all chemotherapy periods and controls without antacid administration. The primary endpoint was the comparison of anorexia incidence during the first cycle of chemotherapy. Secondary endpoints were CINV evaluation and risk factor analysis for the incidence of anorexia using logistic regression analysis. RESULTS: The incidence of anorexia during the first cycle was 54.4% in the control group and 60.3% in the antacid group, without significant differences (p = 0.60). The incidence of nausea was also similar between the groups (p = 1.00). Multivariate analysis suggested that antacid administration was not associated with anorexia. CONCLUSION: Baseline antacid administration does not affect gastrointestinal symptoms associated with CDDP-containing treatment in lung cancer.
• Onset timing and duration of augmented renal clearance in a mixed intensive care unit.
  Ryusei Mikami; Mineji Hayakawa; Shungo Imai; Mitsuru Sugawara; Yoh Takekuma
  Journal of intensive care, 11, 1, 13, 13, 2023年03月23日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Augmented renal clearance (ARC) is associated with lower blood plasma concentrations of renally excreted drugs; however, its time course is unknown. The current study aimed to determine the onset timing/duration of ARC, its risk factors, and its association with clinical outcomes by continuous monitoring of urinary creatinine clearance (CrCl) in critically ill patients. METHODS: Data were retrospectively obtained from the medical records of 2592 critically ill patients admitted to the intensive care unit (ICU) from January 2019 to June 2022 at a tertiary emergency hospital. Among these, patients with continuously measured urinary CrCl were selected and observed over time. We evaluated the onset timing and duration of ARC by plotting Kaplan-Meier curves. Furthermore, by multivariate analyses, factors associated with the onset and persistence of ARC were analyzed, and the association between the ARC time course and clinical outcomes was evaluated. RESULTS: The prevalence of ARC was 33.4% (245/734). ARC onset was within 3 days of admission in approximately half of the cases, and within 1 week in most of the other cases. In contrast, the persistence duration of ARC varied widely (median, 5 days), and lasted for more than a month in some cases. Multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanically assisted ventilation, and vasopressor use as onset factors for ARC. Furthermore, factors associated with ARC persistence such as younger age and higher urinary CrCl on ARC day 1 were detected. The onset of ARC was significantly associated with reduced mortality, but persistent of ARC was significantly associated with fewer ICU-free days. CONCLUSIONS: Despite the early onset of ARC, its duration varied widely and ARC persisted longer in younger patients with higher urinary CrCl. Since the duration of ARC was associated with fewer ICU-free days, it may be necessary to consider a long-term increased-dose regimen of renally excreted drugs beginning early in patients who are predicted to have a persistent ARC.
• Usefulness of the Albumin–Bilirubin Score in Determining the Initial Dose of Voriconazole for Patients with Liver Cirrhosis
  Shunsuke Nashimoto; Shungo Imai; Mitsuru Sugawara; Yoh Takekuma
  Biological and Pharmaceutical Bulletin, 46, 2, 230, 236, Pharmaceutical Society of Japan, 2023年02月01日, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• Use of Japanese big data from electronic medical records to investigate risk factors and identify their high-risk combinations for linezolid-induced thrombocytopenia.
  Yuki Inoue; Yoh Takekuma; Takayuki Miyai; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Shungo Imai
  European journal of clinical pharmacology, 79, 3, 415, 425, 2023年01月30日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Thrombocytopenia is a major event associated with linezolid (LZD) therapy. Factors affecting LZD-induced thrombocytopenia (LIT) have been reported in previous studies. However, several issues pertaining to LIT have not yet been clarified. In the present study, we used Japanese big data to investigate associated factors and their high-risk combinations that influence LIT. METHODS: Patients administered LZD between May 2006 and October 2020 were included in this study. LIT was defined as either a 30% or more reduction from the baseline platelets or platelet values of < 100,000/µL. We evaluated factors affecting LIT and combinations of factors that alter LIT risk according to a decision tree (DT) analysis, a typical machine learning method. RESULTS: We successfully enrolled 1399 patients and LIT occurred in 44.7% of the patients (n = 626). We classified the laboratory data on renal function, LZD duration, age, and body weight (BW) into smaller categories. The results of multivariate analysis showed that prolonged LZD therapy, BW < 45 kg, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, and dialysis were risk factors for LIT. The DT analysis revealed that the highest risk was a combination of LZD duration ≥ 14 days and eGFR < 30 mL/min/1.73 m2. CONCLUSIONS: The present study extracted four risk factors and identified high-risk combinations for LIT. Patients with these risk factors should be closely monitored.
• Prediction and Implications of Edoxaban-Associated Bleeding in Patients after Critical Illness
  Ryusei Mikami; Mineji Hayakawa; Shungo Imai; Kunihiko Maekawa; Kojiro Yamazaki; Mitsuru Sugawara; Yoh Takekuma
  Journal of Clinical Medicine, 12, 3, 860, 860, MDPI AG, 2023年01月21日, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）, In this retrospective study, we aimed to identify the risk factors for bleeding in patients after critical illness during edoxaban treatment. Data from patients who received edoxaban after critical illness at the Emergency Department at a tertiary care hospital were obtained from the hospital medical records. Multivariate analysis revealed the risk factors for edoxaban-associated bleeding. Additionally, we developed an edoxaban-associated bleeding score (EAB score) based on these results. The derived EAB score was compared with the HAS-BLED score using receiver operating characteristic (ROC) curve analysis. Bleeding was observed in 42 of 114 patients (36.8%). We identified the following bleeding predictors (odds ratios, 95% confidence interval, score points) using multivariate analysis: concomitant use of antiplatelet agents (6.759, 2.047–22.32, 2 points), concomitant use of P-glycoprotein inhibitors (3.825, 1.484–9.856, 1 point), prothrombin time (PT)% following edoxaban administration of <75% and ≥60% (2.507, 0.788–7.970, 1 point), and PT% following edoxaban administration of <60% (11.23, 3.560–35.42, 3 points). The ROC curve analysis revealed an area under the curve of 0.826 for the EAB score and 0.625 for the HAS-BLED score. Under appropriate edoxaban dosing regimens in patients after critical illness, a combination of antiplatelet agents, P-gp inhibitors, and a low PT% following edoxaban administration were identified as strong risk factors for bleeding.
• Effects of Body Composition on Renal Function Estimates in Older Patients.
  Soyoko Kaburaki; Shungo Imai; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Yoh Takekuma
  Biological & pharmaceutical bulletin, 46, 11, 1609, 1618, 2023年, ［国内誌］
  英語, 研究論文（学術雑誌）, The modified Cockcroft-Gault (CG) equation, previously developed for an aged-oriented cohort, was validated in a newly obtained dataset. Estimates of creatinine clearance (CCr) using this equation were found to be more accurate than those determined using the conventional CG equation, particularly for patients exceeding 65 years of age. We identified a subset of patients in this cohort whose estimates were inadequate. Using statistical analysis, we found that the deviation from estimates was attributed to a decreased albumin level. In addition, we determined a reduced albumin cutoff value for the modified CG equation to obtain a good estimate. Univariate linear regression analysis was applied to measure the CCr in this cohort and identify parameters related to body composition, and we found that extracellular water (ECW)/total body water (TBW) and body fat (%) were relevant. Using measured values of ECW/TBW and body fat (%), a multivariate linear regression (MLR) estimating equation was developed based on the modified CG equation. This equation was applied to a cohort over 65 years of age, and it was found that a good estimate was obtained for older patients with low albumin levels. Thus, we propose a flow diagram that illustrates conditions for selecting an appropriate estimating equation from among the CG, modified CG, and MLR equations.
• Temporary Severe Neutropenia during Administration of Atezolizumab: A Novel Case Report.
  Ryota Kanno; Yoshitaka Saito; Yoh Takekuma; Hajime Asahina; Mitsuru Sugawara
  Case reports in oncology, 16, 1, 372, 377, 2023年, ［査読有り］, ［国際誌］
  英語, Here, we describe a case of temporary severe neutropenia after atezolizumab monotherapy and its treatment course. Atezolizumab monotherapy was introduced as a 6th-line treatment for a man in his late 60s, who was diagnosed with stage Ⅳ lung adenocarcinoma. The first treatment cycle was administered during hospitalization, and the patient presented with a fever of 37.8°C on the first day. The fever resolved after the administration of acetaminophen and naproxen, and the white blood cell count, neutrophil count, and other white blood cell fractions were normal. However, grade 3 leukopenia and grade 4 neutropenia appeared at the beginning of the third cycle, and treatment was discontinued. After treatment, monocyte count in the leukocyte fraction increased from approximately 10% to 25.6%. Lenograstim 100 μg subcutaneous injection and oral levofloxacin 500 mg once daily were started of onset of neutropenia, and he was hospitalized the next day. Laboratory findings upon admission showed a significant improvement to 5,300/µL for leukocytes and 3,376/µL for neutrophils. Lenograstim was discontinued, with no further decrease in the neutrophil count. Atezolizumab therapy was resumed, and there was no further reduction in leukocyte, neutrophil, or leukocyte fractions over about a 2-year period. Concomitant drugs were maintained during the atezolizumab treatment, suggesting that they did not induce neutropenia. In conclusion, we observed temporary severe neutropenia during atezolizumab monotherapy. Neutrophil recovery with cautious monitoring has enabled longer efficacy. We should consider temporary symptom occurrence in cases of haematological immune-related adverse events.
• Gefitinib-induced Myositis: A Novel Case Report.
  Tatsuhiko Sakamoto; Yoshitaka Saito; Yoh Takekuma; Eiki Kikuchi; Mitsuru Sugawara
  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 143, 7, 617, 620, 2023年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Chemotherapy-induced myositis is a severe adverse event caused by chemotherapeutic agents such as immune checkpoint inhibitors (ICIs) or cytotoxic agents. We experienced a patient with gefitinib-induced myositis with symptoms of muscle cramps and stiffness in the limbs, and reported the treatment process. A 70-year-old woman received four courses of carboplatin (CBDCA)+pemetrexed (PEM)+gefitinib (intravenous CBDCA area under the curve (AUC) 5 and PEM 500 mg/m2, every 3 weeks, and oral gefitinib 250 mg daily), for epidermal growth factor receptor (EGFR) mutation-positive stage IV lung cancer treatment; followed by seven courses of PEM+gefitinib, and continued gefitinib monotherapy thereafter. Myositis occurred 5 months after the initiation of gefitinib monotherapy. She developed strong limb cramps despite regular oral administration of 400 mg acetaminophen three times a day and complained of pain on a numeric rating scale of 10/10. Her creatine kinase (CK) was elevated from the second course of CBDCA+PEM+gefitinib but was stable at grade 1-2 thereafter. However, the muscle symptoms disappeared with CK normalization within a few days of gefitinib discontinuation due to disease progression. The Naranjo Adverse Drug Reaction Scale score was 6, suggesting a probable association. Osimertinib (an EGFR tyrosine kinase inhibitor)-induced myositis has been reported, but similar events were first observed with gefitinib in this case. Consequently, when treating with gefitinib, myositis, including the CK variation, should be monitored and appropriately managed with multidirectional treatment.
• Risk Factor Analysis of Vancomycin-Induced Nephrotoxicity in Paediatric Patients Aged 0-1 Year Using Japanese Medical Database.
  Takayuki Miyai; Yoh Takekuma; Hitoshi Kashiwagi; Yuki Sato; Shunsuke Nashimoto; Mitsuru Sugawara; Shungo Imai
  Biological & pharmaceutical bulletin, 46, 6, 817, 823, 2023年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, Vancomycin (VCM)-induced nephrotoxicity (VIN) is a major side effect in paediatric patients. However, most studies are limited to patients aged 0-18 years. We evaluated the risk factors of VIN in patients aged 0-1 year using Japanese electronic medical record database. We used RWD database which was contained electronic medical records and claims data of approximately 20 million people from 160 medical institutions. We targeted hospitalized patients who were administered VCM between June 2000 and December 2020. VIN was defined by two criteria: Criterion 1 was an increase in serum creatinine (Scr) ≥ 0.5 mg/dL or 50% during VCM treatment period compared to the Scr baseline; and criterion 2 was an increase in Scr ≥50% within seven days or Scr ≥0.3 mg/dL within two days during VCM treatment. The risk factors of VIN were evaluated using multivariate logistic regression analysis. We analysed 446 patients; patients with VIN in Criteria 1 and 2 were 33 and 58, respectively. In Criterion 1, multivariate logistic regression analysis identified four independent factors with p-value <0.05 (VCM concentration ≥20 mg/L, amphotericin B (AMPH-B), piperacillin-tazobactam (TAZ/PIPC), and vasopressor drugs). In Criterion 2, multivariate logistic regression analysis identified concomitant use of vasopressor drugs with p-value <0.05. Therefore, concomitant use of vasopressor drugs was suggested to affect the risk of VIN in patients aged 0-1 year. The findings may help in developing estimation models to assess the risk of VIN in paediatric patients.
• Diabetes mellitus degenerates cisplatin-induced nephrotoxicity in short hydration method: a propensity score-matching analysis
  Yoshitaka Saito; Tatsuhiko Sakamoto; Yoh Takekuma; Masaki Kobayashi; Keisuke Okamoto; Naofumi Shinagawa; Yasushi Shimizu; Ichiro Kinoshita; Mitsuru Sugawara
  Scientific Reports, 12, 1, Springer Science and Business Media LLC, 2022年12月17日, ［査読有り］
  研究論文（学術雑誌）, Abstract
  
  Cisplatin (CDDP)-induced nephrotoxicity (CIN) is dose-limiting. We revealed that co-administration of non-steroid anti-inflammatory drugs and baseline comorbidity of diabetes mellitus (DM) are associated with CIN development in the short hydration method; however, the results were accessorily obtained without appropriate power calculation. This study aimed to demonstrate the influence of DM complications on CIN incidence in a real-world setting. Lung cancer patients receiving CDDP (≥ 75 mg/m²)-containing regimens with a short hydration method (n = 227) were retrospectively evaluated. The patients were divided into control and baseline DM complication groups. The primary endpoint was the evaluation of CIN incidence between the groups. Propensity score-matching was performed to confirm the robustness of the primary analysis results. CIN occurred in 6.8% of control and 27.0% of DM patients, respectively, with a significant difference in all-patient populations (P = 0.001). In addition, variation of serum creatinine and creatinine clearance significantly worsened in DM patients. Similar results were obtained in a propensity-matched population. Multivariate logistic regression analysis found that DM complication is a singular risk factor for CIN development (adjusted odds ratio; 4.31, 95% confidence interval; 1.62–11.50, P = 0.003). In conclusion, our study revealed that baseline DM complications significantly worsen CIN.
• Association between skin immune-related adverse events (irAEs) and multisystem irAEs during PD-1/PD-L1 inhibitor monotherapy
  Atsushi Yamaguchi; Yoshitaka Saito; Katsuya Narumi; Ayako Furugen; Yoh Takekuma; Naofumi Shinagawa; Yasushi Shimizu; Hirotoshi Dosaka-Akita; Mitsuru Sugawara; Masaki Kobayashi
  Journal of Cancer Research and Clinical Oncology, 149, 4, 1659, 1666, Springer Science and Business Media LLC, 2022年11月08日, ［査読有り］
  研究論文（学術雑誌）
• Risk factor analysis for regorafenib-induced severe hypertension in metastatic colorectal cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 30, 12, 10203, 10211, 2022年10月11日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Regorafenib, a multikinase inhibitor, is effective in treating metastatic colorectal cancer (mCRC). Hypertension is a frequently occurring adverse effect caused by regorafenib regardless of previous treatment with vascular endothelial growth factor (VEGF) inhibitors in almost all patients. We identified the risk factors associated with regorafenib-induced severe hypertension. Patients with mCRC (n = 100) who received regorafenib were evaluated retrospectively. The primary endpoint was the evaluation of the risk factors for grade ≥ 3 hypertension. The association between pre-existing hypertension at baseline and grade ≥ 3 hypertension symptoms was also assessed. Patients with pre-existing hypertension at baseline accounted for 55% of the total patients. The starting doses of regorafenib were 160 mg (49.0% of patients), 120 mg (29.0%), and 80 mg (22.0%). The incidence of grade ≥ 3 hypertension was 30.0%. The median time to grade ≥ 3 symptom development was 7 days (range: 1-56 days). Additional antihypertensive treatment was administered to 83.6% of patients who developed hypertension. Logistic regression analyses revealed that baseline pre-existing hypertension complications and previous anti-VEGF treatment for ≥ 700 days were independent risk factors for grade ≥ 3 hypertension development. Further analyses revealed that pre-existing hypertension before anti-VEGF treatment (primary hypertension) was significantly related to the symptom development (adjusted odds ratio, 8.74; 95% confidence interval, 2.86-26.72; P = 0.0001). Our study suggests that pre-existing primary hypertension and previous anti-VEGF treatment for ≥ 700 days are independent risk factors for regorafenib-induced severe hypertension. Deeper understanding of the symptom nature and management can significantly contribute to safer interventions, necessitating further studies.
• 妊娠中にラコサミドを使用し、健児を得た一症例
  北村 聖花; 西村 あや子; 武隈 洋; 齋藤 佳敬; 馬詰 武; 菅原 満
  薬学雑誌, 142, 9, 1031, 1035, (公社)日本薬学会, 2022年09月, ［査読有り］
  日本語
• 薬局薬剤師を対象としたメディアによる「くすりの危険性」に関する報道に起因する患者からの相談応需の実態調査
  今井 俊吾; 阿部 真也; 松井 洸; 柏木 仁; 佐藤 夕紀; 武隈 洋; 吉町 昌子; 菅原 満
  医薬品情報学, 24, 2, 75, 87, (一社)日本医薬品情報学会, 2022年08月, ［査読有り］
  日本語
• Impact of systemic dexamethasone administration on oral mucositis induced by anthracycline-containing regimens in breast cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Tomohiro Oshino; Mitsuru Sugawara
  Scientific reports, 12, 1, 12587, 12587, 2022年07月22日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Influence of Dose Reduction of Prophylactic Dexamethasone on Chemotherapy-induced Nausea and Anorexia in Patients Under 55 Years Old Treated With Anthracycline-containing Regimens.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Mitsuru Sugawara
  Anticancer research, 42, 7, 3753, 3758, 2022年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Risk Factor Analysis for the Occurrence of Severe Adverse Effects in Eribulin Treatment.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Takuro Noguchi; Satoshi Takeuchi; Yasushi Shimizu; Ichiro Kinoshita; Hirotoshi Dosaka-Akita; Mitsuru Sugawara
  Anticancer research, 42, 7, 3693, 3700, 2022年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Combination of Mirogabalin and Duloxetine Attenuates Peripheral Neuropathy by Eribulin: A Novel Case Report
  Yoshitaka Saito; Yoh Takekuma; Tomohiro Oshino; Mitsuru Sugawara
  Case Reports in Oncology, 606, 610, S. Karger AG, 2022年06月10日, ［査読有り］
  研究論文（学術雑誌）, 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.
• Correlation between antibiotic use and antibiotic resistance: A multicenter study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system in Hokkaido, Japan.
  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, 51, 2, 163, 171, 2022年06月04日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Suitability of Oral Rehydration Solution (ORS) for Use in the Cisplatin Short Hydration Method.
  Yoshitaka Saito; Yoh Takekuma; Masaki Kobayashi; Naofumi Shinagawa; Takuro Noguchi; Satoshi Takeuchi; Yasushi Shimizu; Ichiro Kinoshita; Hirotoshi Dosaka-Akita; Mitsuru Sugawara
  Anticancer research, 42, 6, 3185, 3193, 2022年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• 週刊誌に掲載された「危ないクスリ」に関する情報の整理とその適切性評価
  今井 俊吾; 柏木 仁; 佐藤 夕紀; 武隈 洋; 菅原 満
  医薬品情報学, 24, 1, 1, 10, (一社)日本医薬品情報学会, 2022年05月, ［査読有り］
  日本語, 週刊誌に記載された処方箋の「危険性」に関する記事の適切性を、オーストラリアで開発されたマスメディアによる医療・健康記事の質を評価するための指標である「メディアドクター指標」を処方箋等に適用できるよう改変したものを用いて明らかにすることを目的に、2018年1月1日から2021年5月24日までに発行された「週刊朝日」「サンデー毎日」など週刊誌10誌を対象に、「薬剤名や薬効分類を特定可能」かつ「当該薬剤・薬効分類におけるヒトに対する具体的な副作用・有害事象に関して記述」している記事19本(週刊誌6誌)を2名の評価者により評価した。その結果、19本の記事のうち10本はB誌に掲載されたもので、計179種類の薬剤(薬効分類で34種類)の危険性について言及されていた。対象となった19本の記事の内容を9項目について評価者2人が評価した結果、11本で2名とも不満足とした評価項目が半数を超えていた。
• Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer.
  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, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• 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 大規模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
  薬学雑誌, 142, 4, 331, 336, (公社)日本薬学会, 2022年04月, ［招待有り］, ［筆頭著者］
  日本語
• Hepatic drug metabolism in older people with body composition changes
  Soyoko Kaburaki; Eri Yoshimura; Yasushi Miyamoto; Shungo Imai; Hitoshi Kashiwagi; Hidefumi Ueno; Mitsuru Sugawara; Yoh Takekuma
  Geriatrics & Gerontology International, Wiley, 2022年03月30日, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• Evaluation of the strategies to reduce third-generation oral cephalosporins in dentistry at a Japanese academic hospital: An interrupted time series analysis.
  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, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Using Japanese big data to investigate novel factors and their high-risk combinations that affect vancomycin-induced nephrotoxicity.
  Shungo Imai; Shota Kadomura; Takayuki Miyai; Hitoshi Kashiwagi; Yuki Sato; Mitsuru Sugawara; Yoh Takekuma
  British journal of clinical pharmacology, 88, 7, 3241, 3255, 2022年02月01日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Clinical applicability of urinary creatinine clearance for determining the initial dose of vancomycin in critically ill patients.
  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, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Evaluation of risk factors for chemotherapy-induced nausea and vomiting in cisplatin and gemcitabine treatment for biliary tract cancer: acid suppressants do not prevent nausea
  Saito, Y.; Takekuma, Y.; Komatsu, Y.; Sugawara, M.
  Pharmazie, 77, 6, 2022年
  研究論文（学術雑誌）
• Machine Learning-Based Model for Estimating Vancomycin Maintenance Dose to Target the Area under the Concentration Curve of 400-600 mg·h/L in Japanese Patients.
  Takayuki Miyai; Shungo Imai; Eri Yoshimura; Hitoshi Kashiwagi; Yuki Sato; Hidefumi Ueno; Yoh Takekuma; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 45, 9, 1332, 1339, 2022年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• [Case Report on a Woman with Epilepsy Who Took Lacosamide during Pregnancy and Gave Birth to a Healthy Infant].
  Seika Kitamura; Ayako Nishimura; Yoh Takekuma; Yoshitaka Saito; Takeshi Umazume; Mitsuru Sugawara
  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 142, 9, 1031, 1035, 2022年, ［査読有り］, ［国内誌］
  日本語, 研究論文（学術雑誌）, 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.
• [Efficacy Survey of Naldemedine in the Poor-performance Status Group].
  Shintaro Kato; Yoshitaka Saito; Hiroko Onoda; Masayoshi Kumai; Shungo Imai; Kenkichi Tsuruga; Yoh Takekuma; Mitsuru Sugawara
  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 142, 7, 755, 760, 2022年, ［査読有り］, ［国内誌］
  日本語, 研究論文（学術雑誌）, 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.
• Development of a Method of Liquid Chromatography Coupled with Tandem Mass Spectrometry for Simultaneous Determination of Linezolid and Tedizolid in Human Plasma.
  Yuki Sato; Yoh Takekuma; Takayuki Daisho; Hitoshi Kashiwagi; Shungo Imai; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 45, 4, 421, 428, 2022年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Prescription and Therapeutic Drug Monitoring Status of Valproic Acid among Patients Receiving Carbapenem Antibiotics: A Preliminary Survey Using a Japanese Claims Database
  Shungo Imai; Kenji Momo; Hitoshi Kashiwagi; Yuki Sato; Takayuki Miyai; Mitsuru Sugawara; Yoh Takekuma
  Annals of Clinical Epidemiology, 4, 1, 6, 10, Society for Clinical Epidemiology, 2022年, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• A 5% Glucose Solution for the Liquid Formulation Gemcitabine Solvent Decreases Gemcitabine-induced Vascular Pain.
  Kazuki Uchiyama; Yoshitaka Saito; Tatsuhiko Sakamoto; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Anticancer research, 42, 1, 343, 348, 2022年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Therapeutic drug monitoring-enabled long-term use of linezolid for the successful treatment of refractory pyogenic spondylodiscitis without development of thrombocytopenia: A case report.
  Takayuki Daisho; Keisuke Kagami; Koujiro Yamazaki; Nobuhisa Ishiguro; Tsutomu Endo; Masahiko Takahata; Hisataka Suzuki; Mitsuru Sugawara; Yoh Takekuma
  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2021年12月15日, ［査読有り］, ［最終著者, 責任著者］, ［国内誌］
  英語
• Impact of reducing day 1 dexamethasone dose in anthracycline-containing regimens on acute gastrointestinal symptoms associated with breast cancer treatment.
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Mitsuru Sugawara
  Scientific reports, 11, 1, 23298, 23298, 2021年12月02日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Effects of piperacillin/tazobactam or cefepime on folinate dose in patients receiving high-dose methotrexate: A retrospective cohort study using Japanese administrative claims data.
  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, 28, 7, 10781552211034703, 10781552211034703, 2021年10月18日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Severe Hypertriglyceridemia Induced by Docetaxel: A Novel Case Report
  Yoshitaka Saito; Yoh Takekuma; Takashi Takeshita; Mitsuru Sugawara
  Case Reports in Oncology, 14, 3, 1277, 1282, 2021年09月09日, ［査読有り］
  研究論文（学術雑誌）
• 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, ［査読有り］, ［最終著者, 責任著者］
  日本語
• レセプトデータに基づくクローン病新規ブデソニド徐放性製剤の実態調査
  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］, ［最終著者, 責任著者］
  日本語, 研究論文（学術雑誌）
• 薬局薬剤師による「患者への聞き取り」に基づいて実施された疑義照会の実態解明と医療安全への貢献度評価
  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］
  日本語, 研究論文（学術雑誌）
• Utilization and application for medical big data to clinical setting
  Yoh Takekuma; Kenji Momo
  Yakugaku Zasshi, 141, 2, 163, 164, Pharmaceutical Society of Japan, 2021年02月01日
  日本語, 研究論文（学術雑誌）
• Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation.
  Yoshitaka Saito; Yoh Takekuma; Yoshito Komatsu; Mitsuru Sugawara
  Biological & pharmaceutical bulletin, 44, 12, 1819, 1823, 2021年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• cAMP Signaling Pathway Prevents Dasatinib-Induced Vascular Hyperpermeability
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Pharmaceutical Intervention According to Strict Management System Can Normalize Decreased Serum Calcium Level by Denosumab and Prevent Its Aggravation
  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］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Severe hypertriglyceridemia induced by S-1: Subsequent case series of four patients and further review of the literature
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Sarcopenia in a patient with most serious complications after highly invasive surgeries treated with nutrition, rehabilitation, and pharmacotherapy: a case report
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Risk factor analysis for taxane-associated acute pain syndrome under the dexamethasone prophylaxis
  Saito, Y.; Takekuma, Y.; Kobayashi, M.; Sakamoto, T.; Yamashita, H.; Sugawara, M.
  Support Care Cancer, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Pregabalin Attenuates Carboplatin-Induced Akathisia-Like Neuropathy: A Novel Case Report
  Saito, Yoshitaka; Takekuma, Yoh; Furuta, Megumi; Sugawara, Mitsuru
  Case Reports in Oncology, 1418, 1421, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Preexisting autoimmune disease is a risk factor for immune-related adverse events: a meta-analysis
  Yamaguchi, A.; Saito, Y.; Okamoto, K.; Narumi, K.; Furugen, A.; Takekuma, Y.; Sugawara, M.; Kobayashi, M.
  Support Care Cancer, Research Square Platform LLC, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）,
  Purpose Patients with preexisting autoimmune disease (PAD) are often excluded from clinical trials assessing immune checkpoint inhibitors (ICIs). Therefore, the safety of ICI therapy in patients with PAD remains unclear. Herein, we evaluated the incidence of immune-related adverse events (irAEs) in patients with PAD when compared with non-PAD patients.Methods We searched MEDLINE/PubMed, Web of Science, and Google Scholar for eligible studies from inception to January 2021. Observational studies reporting the incidence of irAEs in patients with and without PAD were included. We then performed a meta-analysis of eligible studies using forest plots. The primary endpoint of this study was the incidence rate of irAEs between patients with and without PAD.Results We identified three prospective and three retrospective studies involving 206 patients with PAD and 3078 patients without PAD. In the meta-analysis, 128 patients with PAD (62.1%) experienced irAEs, which occurred in 51.9% of non-PAD patients, resulting in an odds ratio (OR) of 2.14 (95% confidence interval [CI] 1.58–2.89). In the subgroup analysis, the incidence of irAEs was significantly higher in patients with PAD (OR = 2.19, 95% CI [1.55–3.08]). Furthermore, no significant heterogeneity or publication bias was detected, indicating that our meta-analysis could be generalized to clinical settings.Conclusion This meta-analysis demonstrated that PAD was a risk factor for irAE incidence. These results suggest that monitoring the occurrence of irAEs in patients with PAD is required to manage irAEs appropriately.
• Investigation of the risk factors of vomiting during linezolid therapy: a retrospective observational study
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Investigation of the Real-World Situation and Risk Factors Associated with Olanzapine Prescribed to Diabetes Patients by Using a Japanese Claims Database
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Implementation Status of Liver Function Tests for Monitoring Benzbromarone-Induced Hepatotoxicity: An Epidemiological Survey Using the Japanese Claims Database
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Factors affecting creatine phosphokinase elevation during daptomycin therapy using a combination of machine learning and conventional methods
  Imai, S.; Kashiwagi, H.; Sato, Y.; Miyai, T.; Sugawara, M.; Takekuma, Y.
  Br J Clin Pharmacol, 88, 3, 1211, 1222, Wiley, 2021年, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Alleviation of Abdominal Pain due to Irinotecan-Induced Cholinergic Syndrome Using Loperamide: A Case Report
  Uchiyama, K.; Saito, Y.; Takekuma, Y.; Yuki, S.; Sugawara, M.
  Case Rep Oncol, 14, 2, 806, 811, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）
• An imaging approach for determining the mechanism of enhancement of intestinal absorption of an L-theanine supplement
  Sato, Y.; Yamaguchi, K.; Ogawa, M.; Takekuma, Y.; Sugawara, M.
  PLoS One, 16, 6, e0253066, 2021年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Clinical outcomes of intervention for carbapenems and anti-methicillin-resistant Staphylococcus aureus antibiotics by an antimicrobial stewardship team
  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, Elsevier BV, 2021年, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• A cross-sectional survey of hospitalization and blood tests implementation status in patients who received tolvaptan under 75 years of age using a Japanese claims database
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Evaluation of Chemotherapy Regimen Management Practice by Oncology-Specialized and Non-specialized Pharmacists Collaboration
  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］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Safety Evaluation of Initial CT-P6 Administration for 30 min during the Switch from Reference Trastuzumab in Maintenance Infusion: A Multicenter Observational Study
  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］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Hypertriglyceridemia Induced by Fluorouracil: A Novel Case Report
  Saito, Y.; Takekuma, Y.; Yuki, S.; Komatsu, Y.; Sugawara, M.
  Case Rep Oncol, 14, 1, 207, 211, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）
• A new system to evaluate characteristics of Niemann-Pick C1 Like 1-mediated cholesterol transport using Xenopus laevis oocytes
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Benzodiazepine Concentrations in the Breast milk and Plasma of Nursing Mothers: Estimation of Relative Infant Dose
  Nishimura, A.; Furugen, A.; Umazume, T.; Kitamura, S.; Soma, M.; Noshiro, K.; Takekuma, Y.; Sugawara, M.; Iseki, K.; Kobayashi, M.
  Breastfeed Med, 16, 5, Mary Ann Liebert Inc, 2021年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Construction of a Risk Prediction Model of Extended Release Oxycodone Tablet-Induced Nausea and Clarification of Predictive Factors
  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］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Probiotic Prescription Status of Pediatric Patients with Otitis Media Receiving Oral Amoxicillin or Amoxicillin/Clavulanate from April 2016 to March 2017 Using a Japanese Health Insurance Claims Database
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell lung cancer
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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, ［査読有り］
  日本語, 研究論文（学術雑誌）
• 救急/集中治療領域における薬剤師介入の実態と有害事象回避による潜在的な医療経済評価
  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］
  日本語, 研究論文（学術雑誌）
• 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］
  日本語, 研究論文（学術雑誌）
• Pharmacokinetics of mycophenolic acid after haplo-hematopoietic stem cell transplantation in Japanese recipients
  Uchiyama, K.; Saito, Y.; Takekuma, Y.; Sugita, J.; Teshima, T.; Sugawara, M.
  J Oncol Pharm Pract, 1078155220980815, 1078155220980815, SAGE Publications, 2020年, ［査読有り］
  英語, 研究論文（学術雑誌）, 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.
  
  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 AUC_6-12h/AUC_0-12h.
  
  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.
  
  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.
  
  
• Pharmaceutical Care Contributes to the Advanced Management of Patients Receiving Immune Checkpoint Inhibitors
  Saito, Y.; Uchiyama, K.; Sakamoto, T.; Yamazaki, K.; Kubota, K.; Takekuma, Y.; Komatsu, Y.; Sugawara, M.
  Biol Pharm Bull, 43, 12, 1969, 1974, Pharmaceutical Society of Japan, 2020年, ［査読有り］
  英語, 研究論文（学術雑誌）
• A Risk Prediction Flowchart of Vancomycin-Induced Acute Kidney Injury to Use When Starting Vancomycin Administration: A Multicenter Retrospective Study
  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, MDPI AG, 2020年, ［査読有り］
  英語, 研究論文（学術雑誌）, 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.
• Hypertriglyceridemia induced by S-1: A novel case report and review of the literature
  Saito, Y.; Takekuma, Y.; Komatsu, Y.; Sugawara, M.
  J Oncol Pharm Pract, 27, 4, 1078155220956691, 1078155220956691, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Prescription of Colchicine with Other Dangerous Concomitant Medications: A Nation-Wide Survey Using the Japanese Claims Database
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone
  Nashimoto, S.; Takekawa, Y.; Takekuma, Y.; Sugawara, M.; Sato, Y.
  Drug Metab Pharmacokinet, 35, 6, 527, 533, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment
  Saito, Y.; Takekuma, Y.; Kobayashi, M.; Komatsu, Y.; Sugawara, M.
  Support Care Cancer, 29, 6, 3277, 3285, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Association of the ward pharmacy service with active implementation of therapeutic drug monitoring for vancomycin and teicoplanin-an epidemiological surveillance study using Japanese large health insurance claims database
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Comparison of interactions between warfarin and cephalosporins with and without the N-methyl-thio-tetrazole side chain
  Imai, S.; Kadomura, S.; Momo, K.; Kashiwagi, H.; Sato, Y.; Miyai, T.; Sugawara, M.; Takekuma, Y.
  J Infect Chemother, 26, 11, 1224, 1228, Elsevier BV, 2020年, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• A cross-sectional exploratory survey on occurrence of triple-whammy prescription pattern in Japan
  Imai, S.; Momo, K.; Kashiwagi, H.; Miyai, T.; Sugawara, M.; Takekuma, Y.
  Int J Clin Pharm, 42, 5, 1369, 1373, Springer Science and Business Media LLC, 2020年, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Transfer of orally administered hyaluronan to the lymph
  Sato, Y.; Joumura, T.; Takekuma, Y.; Sugawara, M.
  Eur J Pharm Biopharm, 154, 210, 213, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Validation of the usefulness of artificial neural networks for risk prediction of adverse drug reactions used for individual patients in clinical practice
  Imai, S.; Takekuma, Y.; Kashiwagi, H.; Miyai, T.; Kobayashi, M.; Iseki, K.; Sugawara, M.
  PLoS One, 15, 7, e0236789, e0236789, Public Library of Science (PLoS), 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Serotonin Syndrome Developing Immediately after the Initiation of Low-Dose Methadone Therapy: A Case Report
  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］
  英語, 研究論文（学術雑誌）
• Interaction Between Piperacillin/Tazobactam and Warfarin: a Single-Center Retrospective Single-Arm Cohort Study
  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］
  英語, 研究論文（学術雑誌）
• Nonsteroidal anti-inflammatory drugs use in patients with chronic kidney disease are often prescribed from different clinicians than those who diagnosed them
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Possibility for Dose Optimization of Pazopanib from Its Plasma Concentration in Japanese Patients with Cancer
  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］, ［国内誌］
  英語, 研究論文（学術雑誌）, 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.
• A New Algorithm Optimized for Initial Dose Settings of Vancomycin Using Machine Learning
  Imai, Shungo; Takekuma, Yoh; Miyai, Takayuki; Sugawara, Mitsuru
  Biological and Pharmaceutical Bulletin, 43, 1, 188, 193, 2020年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Influence of gastrointestinal activity on the absorption of nilotinib
  Sasaki, M.; Aoyama, T.; Sugawara, M.; Takekuma, Y.
  Drug Metab Pharmacokinet, 35, 1, 102, 110, 2020年, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Enhancement of intestinal absorption of coenzyme Q10 using emulsions containing oleyl polyethylene acetic acids
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Effect of palonosetron and dexamethasone administration on the prevention of gastrointestinal symptoms in hepatic arterial chemoembolization with epirubicin
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Continuous Cytostatic Effects of BCR-ABL Tyrosine Kinase Inhibitors (TKIs) after Washout in Human Leukemic K562 Cells.
  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］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）
• 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］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• 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ガランタミン投与が有効だった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］
  日本語, 研究論文（学術雑誌）, 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。
• Higher incidence of acute kidney injury in patients treated with piperacillin/tazobactam than in patients treated with cefepime: a single-center retrospective cohort study.
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Improvement of renal function estimation equations for elderly Japanese people.
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Enhancement of lymphatic transport of lutein by oral administration of a solid dispersion and a self-microemulsifying drug delivery system.
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h between α-tocopherol and ezetimibe.
  Nashimoto S; Sato Y; Takekuma Y; Sugawara M
  Biopharmaceutics & drug disposition, 38, 4, 280, 289, 2017年05月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 耳鼻咽喉科領域におけるアレルギー性咳嗽症状を有する患者に対する抗アレルギー薬併用の実態調査
  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］, ［筆頭著者, 責任著者］
  日本語, 研究論文（学術雑誌）
• 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］
  英語, 研究論文（学術雑誌）
• An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1
  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］
  英語, 研究論文（学術雑誌）
• Difference in the Dissolution Behaviors of Tablets Containing Polyvinylpolypyrrolidone (PVPP) Depending on Pharmaceutical Formulation After Storage Under High Temperature and Humid Conditions
  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］
  英語, 研究論文（学術雑誌）
• Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose etoposide, cyclophosphamide and total body irradiation regimen before allogeneic hematopoietic stem cell transplantation.
  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］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Schedule-Dependent Cytotoxicity of Etoposide and Cyclophosphamide in P-Glycoprotein-Expressing Human Leukemic K-562 Cells
  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］
  英語, 研究論文（学術雑誌）
• 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
  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］, ［筆頭著者, 責任著者］
  日本語, 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。
• Emulsification Using Highly Hydrophilic Surfactants Improves the Absorption of Orally Administered Coenzyme Q10
  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］
  英語, 研究論文（学術雑誌）
• Intracellular Uptake Mechanism of Lutein in Retinal Pigment Epithelial Cells
  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］
  英語, 研究論文（学術雑誌）
• Schedule-Dependent Cytotoxicity of Etoposide (VP-16) and Cyclophosphamide in Leukemia Cell Line K-562
  Yuki Tazawa; Kazunori Matsumura; Yoh Takekuma; Mitsuru Sugawara
  BIOLOGICAL & PHARMACEUTICAL BULLETIN, 35, 7, 1132, 1136, 2012年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 効果発現パターンにより抗がん薬を分類するための基礎的検討
  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］
  日本語, 研究論文（学術雑誌）
• Mutual Inhibition between Carvedilol Enantiomers during Racemate Glucuronidation Mediated by Human Liver and Intestinal Microsomes
  Yoh Takekuma; Keiji Yagisawa; Mitsuru Sugawara
  BIOLOGICAL & PHARMACEUTICAL BULLETIN, 35, 2, 151, 163, 2012年02月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Penetration of linezolid into rabbit intervertebral discs and surrounding tissues
  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］
  英語, 研究論文（学術雑誌）
• 高度腎機能障害患者におけるリネゾリドの体内動態
  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］
  日本語, 研究論文（学術雑誌）
• Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation
  Hitoshi Kashiwagi; Kojiro Yamazaki; Yoh Takekuma; Vadivel Ganapathy; Mitsuru Sugawara
  AMINO ACIDS, 36, 2, 219, 230, 2009年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• THERAPEUTIC DRUG MONITORING SAFELY SPARES DOSES OF MYCOPHENOLATE MOFETIL IN MIDDLE-TERM RENAL ALLOGRAFT RECIPIENTS
  Yoh Takekuma
  Transplant International, 2009年
  研究論文（学術雑誌）
• 免疫抑制剤投与量調整にきわめて難渋した乳児腎移植症例
  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
  日本語, 研究論文（学術雑誌）, 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］, ［最終著者, 責任著者］
• 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
  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］
  日本語, 研究論文（学術雑誌）, 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。
• Stereoselective metabolism of racemic carvedilol by UGT1A1 and UGT2B7, and effects of mutation of these enzymes on glucuronidation activity
  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］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Evaluation of effects of polymorphism for metabolic enzymes on pharmacokinetics of carvedilol by population pharmacokinetic analysis
  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］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters
  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］
  英語, 研究論文（学術雑誌）
• Difference between Pharmacokinetics of Mycophenolic acid (MPA) in Rats and that in Humans is caused by Different affinities of MRP2 to a glucuronized form
  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］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• 神経因性疼痛に対する酢酸フレカイニドの鎮痛効果と血中濃度の関係
  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］
  日本語, 研究論文（学術雑誌）
• 小児腎移植におけるSteroid Avoidance免疫抑制法の検討
  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
  日本語
• Contribution of polymorphisms in UDP-glucuronosyltransferase and CYP2D6 to the individual variation in disposition of carvedilol
  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］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations
  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］
  英語, 研究論文（学術雑誌）
• Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites.
  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］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites
  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］
  英語, 研究論文（学術雑誌）
• がん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; 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］, ［筆頭著者］
  日本語, 研究論文（学術雑誌）, 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
• Absorption of ester prodrugs in caco-2 and rat intestine models
  He, X; M Sugawara; Y Takekuma; K Miyazaki
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 48, 7, 2604, 2609, 2004年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The variability of liver graft function and urinary 6 beta-hydroxycortisol to cortisol ratio during liver regeneration in liver transplant recipients
  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］
  英語, 研究論文（学術雑誌）
• 生体部分肝移植患者におけるLinezolid(Zyvox)の体内動態
  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］
  日本語, 研究論文（学術雑誌）, 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
• A new system for the prediction of drug absorption using a pH-controlled Caco-2 model: Evaluation of pH-dependent soluble drug absorption and pH-related changes in absorption
  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］
  英語, 研究論文（学術雑誌）
• Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts
  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］
  英語, 研究論文（学術雑誌）
• An in vitro system for prediction of oral absorption of relatively water-soluble drugs and ester prodrugs
  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］
  英語, 研究論文（学術雑誌）
• 心筋保護液の安定性と使用期間の検討
  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］, ［筆頭著者］
  日本語, 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...
• 0.625%洗眼用イソジン液の安定性に関する検討
  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］, ［筆頭著者］
  日本語, 研究論文（学術雑誌）, 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℃.
• Inhibitory Effects of Basic Drugs on the Sodium-Dependent Transport of L-Alanine via System B° in the Small Intestine
  Mitsuru Sugawara; Masaya Kato; Mayumi Kitakubo; Yoh Takekuma; Vadivel Ganapathy; Katsumi Miyazaki
  Drug Metabolism And Pharmacokinetics, 18, 3, 186, 193, 3, 2003年02月01日, ［査読有り］
  英語, 研究論文（学術雑誌）
• Age- and gender-related differences in carbohydrate concentrations of alpha(1)-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities
  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］
  英語, 研究論文（学術雑誌）
• Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection
  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］
  英語, 研究論文（学術雑誌）
• Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population
  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］
  英語, 研究論文（学術雑誌）
• 生体肝移植患者における持続血液ろ過透析(CHDF)施行時のタクロリムス及びフルコナゾールの血中動態
  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, (一社)日本TDM学会, 2002年01月, ［査読有り］
  日本語, 研究論文（学術雑誌）, 生体部分肝移植を受けタクロリムス(TAC)およびフルコナゾール(FCZ)を投与した患者4名(女3名・男1名,35〜55歳)について持続血液濾過透析(CHDF)に伴う薬物体内動態の影響について検討した.全血中TAC濃度はCHDF中止に伴う著しい上昇は認められなかった.一方,血漿中FCZ濃度はCHDF非施行患者では投与量依存的に変動したが,CHDF施行患者ではFCZ投与量を増量したにも拘わらず,血漿中濃度は著しく推移し最低有効血中濃度を維持することが難しいことが判明した.このことから,CHDF施行によりFCZ濃度が著しい影響を受けることが明らかになり,CHDF施行患者に対してFCZを適正に使用するためにはCHDF施行時の体内動態に基づいて投与を行うことが必要であることが示唆された
• Genotyping of the N-acetyltransferase2 Polymorphism in the Prediction of Adverse Drug Reactions to Isoniazid in Japanese Patients
  Masahiro Hiratsuka; Yoh Takekuma; Masaki Matsuura; Kaori Narahara; Tomoko Inoue; Samar Hamdy Ismail; Naomi Endo
  Drug Metabolism and Pharmacokinetics, 17, 4, 357, 362, 4, 2002年, ［査読有り］
  英語, 研究論文（学術雑誌）
• The Effect of Cisapride on Tacrolimus Pharmacokinetics in a Renal Transplant Patient
  Kishino, S.; Koshinami, Y.; Komai, T.; Suda, N.; Takekuma, Y.; Takeuchi, I.; Koyanagi, T.; Miyazaki, K.
  The Japanese Journal of Therapeutic Drug Monitoring, 18, 4, 349, 354, 2001年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 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及び抗真菌剤の血中動態
  越浪 由加; 須田 範行; 武隈 洋; 小林 道也; 岸野 吏志; 森本 裕二; 丸藤 哲; 古川 裕之; 藤堂 省; 宮崎 勝巳
  TDM研究, 18, 2, 169, 170, (一社)日本TDM学会, 2001年04月
  日本語
• Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration
  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］
  英語, 研究論文（学術雑誌）
• A general approach for the prediction of the intestinal absorption of drugs: Regression analysis using the physicochemical properties and drug-membrane electrostatic interaction
  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］
  英語, 研究論文（学術雑誌）
• 北大病院における処方オーダリングシステム (4) 薬剤情報提供システムの導入
  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］
  日本語, 研究論文（学術雑誌）, 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.
• 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
  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
  日本語, 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.
• Predicting the Intestinal Absorption of Anionic Drugs from Their Physicochemical Properties
  Mitsuru Sugawara; Yoh Takekuma; Michiya Kobayashi; Ken Iseki; Katsumi Miyazaki
  Pharmacy and Pharmacology Communications, 1, 10, 491, 493, 1995年, ［査読有り］
  英語, 研究論文（学術雑誌）

• 睡眠薬使用に関する院内ガイドライン改訂に合わせた不眠時指示薬変更の効果
  熊井 正貴; 金森 怜; 植田 孝介; 沖 洋充; 武隈 洋; 菅原 満, 北海道病院薬剤師会誌, 109, 7, 10, 2025年11月
  (一社)北海道病院薬剤師会, 日本語
• 薬剤師のための消化管の知識(No.8) 消化管の蠕動運動と胆汁分泌が薬物の吸収過程に及ぼす影響
  武隈 洋, Helicobacter Research, 29, 1, 89, 92, 2025年06月
  (株)先端医学社, 日本語
• トランスポーターの輸送活性評価が可能な空腸上皮細胞単層培養系の確立
  笹川義樹; 神嶋莉穂; 柏木仁; 佐藤夕紀; 梨本俊亮; 武隈洋; 菅原満; 菅原満, 日本薬学会年会要旨集(Web), 145th, 2025年
• P-gp基質性評価のためのP-gp高発現細胞樹立とその中分子化合物への応用
  柏木仁; 山田隼大; 王子谷健太; 佐藤夕紀; 梨本俊亮; 渡邉瑞貴; 廣瀬友靖; 廣瀬友靖; 岩月正人; 岩月正人; 砂塚敏明; 砂塚敏明; 金光佳世子; 石井真由美; 渡邊恵里; 宮地弘幸; 武隈洋; 菅原満; 菅原満, 日本薬学会年会要旨集(Web), 145th, 2025年
• 血小板によるアミノ酸トランスポーターSNAT4の輸送活性変動
  柏木仁; 佐藤夕紀; 梨本俊亮; 今井俊吾; 武隈洋; 菅原満; 菅原満, 日本薬学会年会要旨集(Web), 145th, 2025年
• 日本の集中治療室における過大腎クリアランス予測スコアの開発と検証
  三上龍生; 三上龍生; 今井俊吾; 早川峰司; 佐藤夕紀; 柏木仁; 梨本俊亮; 菅原満; 武隈洋, 日本薬学会年会要旨集(Web), 145th, 2025年
• トラブルシューティングに効果的な電子マニュアルの作成・運用
  小柳 遼; 川岸 亨; 水口 貴史; 山崎 浩二郎; 武隈 洋; 菅原 満, 北海道病院薬剤師会誌, 107, 7, 9, 2024年11月
  (一社)北海道病院薬剤師会, 日本語
• 医薬品の在庫管理における医療機器の導入効果
  山崎 浩二郎; 久保田 康生; 川岸 亨; 武隈 洋; 菅原 満, 北海道病院薬剤師会誌, 104, 17, 19, 2023年04月
  近年バイオ医薬品の開発が進み、高額な医薬品が次々に上市されている。当院のような急性期病院においては、治療の変更や中止により、その高額な医薬品を使用しなくなることがあり、使用しなかった医薬品は不動在庫となり期限切れを起こすことがあり、これは病院経営的に大きな損失となる。そこで当院では、特に高額な冷所保管医薬品をリフレッシュできる医薬品専用保冷庫「Cubixx」(スズケングループ)を2019年2月に導入した。また、治療の変更や中止により投与中止となった一包化の内服薬を分別し再利用する目的で「TABSORT」(YUYAMA社)を2021年3月に導入した。Cubixx導入後3年間の各年度に7～9種類の医薬品をリフレッシュし、その効果として、薬価にして合計100万円以上の損失を未然に防ぐことができた。TABSORT導入後1年間に再利用することができた錠剤は延べ66701剤(薬価にして252万円)であった。, (一社)北海道病院薬剤師会, 日本語
• 医薬品の在庫管理における医療機器の導入効果
  山崎 浩二郎; 久保田 康生; 川岸 亨; 武隈 洋; 菅原 満, 北海道病院薬剤師会誌, 104, 17, 19, 2023年04月
  (一社)北海道病院薬剤師会, 日本語
• 高齢者における体組成の変化と薬物動態の関連
  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, ［責任著者］
  日本語, 会議報告等
• アフリカツメガエル卵母細胞を用いたNPC1L1による基質輸送機構の解析
  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
  日本語, 会議報告等
• 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
  日本語, 会議報告等
• 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
  日本語, 会議報告等
• 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
  会議報告等
• 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
  会議報告等
• 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
  日本語, 会議報告等
• 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
  日本語, 会議報告等
• Xenopus laevis oocyteを用いたコレステロールトランスポーターNiemann-Pick C1-Like1(NPC1L1)発現系の構築
  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
• 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
• 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
• 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
• 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
• 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
  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
  (一社)日本TDM学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 消化管活動性がニロチニブの吸収性に及ぼす影響
  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
  日本語
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  (公社)日本薬剤学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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(CD-ROM), 138th, 4, ROMBUNNO.27C‐am03, 51, 2018年03月
  (公社)日本薬学会, 日本語
• 新しい錠剤包装ESOP(easy seal open pack)の使用感とその改良に向けた調査研究
  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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  英語, 研究発表ペーパー・要旨（国際会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  (公社)日本薬学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  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
  (公社)日本整形外科学会, 日本語
• 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
  (公社)日本薬剤学会, 日本語
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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］, ［筆頭著者, 責任著者］
  記事・総説・解説・論説等（その他）
• 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, ［招待有り］, ［筆頭著者, 責任著者］
  記事・総説・解説・論説等（その他）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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］, ［筆頭著者, 責任著者］
  記事・総説・解説・論説等（その他）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  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, ［招待有り］, ［筆頭著者, 責任著者］
  記事・総説・解説・論説等（その他）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
  (一社)日本医薬品情報学会, 日本語
• 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
  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。, (公財)臨床薬理研究振興財団, 日本語
• 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
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 実務実習をより良くするために(12)実務実習を効果的に実施するための事前学習と実習後のアドバンストプログラムの開発
  菅原 満; 武隈 洋; 柴山 良彦, 医薬ジャーナル, 51, 5, 145, 149, 2015年05月
  医薬ジャーナル社, 日本語
• 実務実習をより良くするために 実務実習を効果的に実施するための事前学習と実習後のアドバンストプログラムの開発
  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
  (株)医薬ジャーナル社, 日本語
• 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
  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, TDM研究, 32, 2, 151, 151, 2015年05月
  (一社)日本TDM学会, 日本語
• 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
  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
  (公社)日本薬剤学会, 日本語
• 乳剤化によるコエンザイムQ10の消化管吸収改善
  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
  (公社)日本薬剤学会, 日本語
• 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
  武隈 洋; 石坂 悠; 平野 卓哉; 野田 敏宏; 熊井 惠美; 菅原 満, アレルギー, 64, 3-4, 576, 576, 2015年04月
  (一社)日本アレルギー学会, 日本語
• Niemann-Pick C1 Like-1(NPC1L1)を標的とした乳剤化による難吸収性物質の吸収改善
  竹川 悠人; 佐藤 夕紀; 鷲見 正人; 武隈 洋; 菅原 満, 日本薬学会年会要旨集, 135年会, 4, 76, 76, 2015年03月
  (公社)日本薬学会, 日本語
• UDP-グルクロン酸転移酵素の生細胞と細胞破砕液での代謝活性の比較
  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
  研究発表ペーパー・要旨（全国大会，その他学術会議）
• 28-O4PM-10 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(薬物療法(その他)3,一般演題(口頭),新時代を拓く医療薬学フロンティア)
  石坂 悠; 武隈 洋; 吉村 恵理; 吉田 憲史; 小嶋 希望; 上野 英文; 菅原 満, 日本医療薬学会年会講演要旨集, 24, 244, 244, 2014年08月25日
  日本医療薬学会, 日本語
• UGT1A1 p.P364L変異体および UGT2B7 p.P366L変異体の光学異性体認識性
  依田めぐみ; 佐藤夕紀; 鷲見正人; 武隈洋; 菅原満, 第28回北海道薬物作用談話会（札幌）, 2014年07月19日
• 抗ウイルス薬 リバビリンのトランスポーターを介した消化管吸収の解析
  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
• 中等量エトポシド(VP‐16)/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンにおけるVP‐16のPK/PD解析による投与量の最適化に関する検討
  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
  日本語
• 6年制薬学教育に係る基盤構築
  武隈 洋, 日本薬学会北海道支部第141回例会（札幌）, 2014年05月24日, ［招待有り］
  日本語, 研究発表ペーパー・要旨（全国大会，その他学術会議）
• 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
• 臨床応用を目指したHPLC-UV法による血中imatinib定量法の確立
  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
  (一社)日本TDM学会, 日本語
• 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
• Caco-2細胞におけるNPC1L1を介したコレステロール輸送の特徴
  阿部沙也華; 佐藤夕紀; 鷲見 正人; 武隈 洋; 菅原 満, 第27回北海道TDM研究会研究発表会（札幌）, 2013年11月30日
• 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
• 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
• 土-10-O14-09 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(薬物動態,一般演題(口頭)14,再興、再考、創ろう最高の医療の未来)
  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
  日本医療薬学会, 日本語
• 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
  (一社)日本医薬品情報学会, 日本語
• 難吸収性ポリフェノールの乳剤化によるバイオアベイラビリティ改善
  星山博俊; 佐藤夕紀; 鷲見正人; 武隈洋; 菅原満, 第27回北海道薬物作用談話会（江別）, 2013年07月20日
• 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
• 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
• hOATPs/rOatps を介するミコフェノール酸グルクロナイドの輸送特性の種差
  坂本達彦; 鷲見正人; 佐藤夕紀; 武隈洋; 菅原満, 日本薬学会北海道支部第140回例会（札幌）, 2013年05月
• 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
  (公社)日本薬剤学会, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• 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
• 一包化調剤時におけるスタチン製剤の保存安定性
  高地里佳; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満, 第26回北海道薬物作用談話会（札幌）, 2012年07月
• テアニンの脳移行に関与するトランスポーター
  川守田渉; 亀田佑生; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満, 第26回北海道薬物作用談話会（札幌）, 2012年07月
• 粒子径に着目した CoQ10 の乳剤化による吸収改善
  能登数馬; 佐藤夕紀; 武隈 洋; 菅原 満, 日本薬学会北海道支部第138回例会（札幌）, 2012年06月
• P糖蛋白質(P-gp)発現白血病由来細胞を用いたエトポシド(VP-16)/シクロホスファミド(CY)曝露順序の殺細胞効果に及ぼす影響
  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
  (公社)日本薬学会, 日本語
• 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
  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
  日本語
• 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
  (株)インフォノーツパブリッシング, 日本語
• エトポシド/シクロホスファミド併用の殺細胞効果に及ぼす曝露順序の影響 ～白血病由来 K-562 細胞及び P-糖タンパク質発現株を用いた検討～
  田澤佑基; 臼窪一平; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満, 日本薬学会北海道支部第137回例会（札幌）, 2011年12月
• 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
  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
  (一社)日本TDM学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  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
• 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; 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
• 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
  (株)薬事新報社, 日本語
• TDM実践シリーズ 免疫抑制剤 シクロスポリン・タクロリムス
  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
  (株)薬事新報社, 日本語
• 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
  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
  (公社)日本薬学会, 日本語
• PK/PD概念に基づいた抗がん剤の分類
  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
  (公社)日本薬学会, 日本語
• 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
  武隈 洋; 小林 正紀; 山田 勇磨; 板垣 史郎; 吉田 和幸; 井関 健; 菅原 満, 日本薬学会年会要旨集, 130年会, 4, 346, 346, 2010年03月
  (公社)日本薬学会, 日本語
• TDM実践シリーズ（17）免疫抑制剤①ミコフェノール酸モフェチル
  武隈 洋; 菅原 満; 小林道也; 唯野貢司; 野村憲和, 薬事新報, 2623, 9, 14, 2010年
• 腎移植患者において腎機能の変動がミコフェノール酸体内動態に与える影響
  大谷 薫; 武隈 洋; 原田幸子; 福澤信之; 下田直彦; 三浦正義; 菅原 満; 野々村克也; 井関 健, 第23回北海道TDM研究会研究発表会（札幌）, 2009年11月
• ボリコナゾールの血漿中濃度および髄液移行性をモニタリングした脳クリプトコックス症例
  田島宏恵; 武隈 洋; 沖 洋充; 八島萌美; 秋本幸子; 菅原 満; 井関 健, 第23回北海道TDM研究会研究発表会（札幌）, 2009年11月
• 腎移植レシピエントにおけるミコフェノール酸の治療的薬物モニタリングの臨床応用―薬物動態学および薬力学的解析を用いて―
  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
  日本語
• 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
  武隈 洋; 加藤 貴志; 漆畑 英樹; 小松 幹; 高畑 雅彦; 菅原 満; 三浪 明男; 井関 健, TDM研究, 26, 3, s149, s149, 2009年06月
  (一社)日本TDM学会, 日本語
• テイコプラニン初期投与設計への薬剤師介入の効果
  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
  (一社)日本TDM学会, 日本語
• 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
  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
  (一社)日本TDM学会, 日本語
• 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
• 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
• 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
• 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
  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
  (公社)日本整形外科学会, 日本語
• 抗MRSA薬テイコプラニンの初期投与設計による適正使用への関わり
  木村 俊也; 山崎 浩二郎; 西村 あや子; 坪内 孝敏; 横田 亜季; 小笠原 貴子; 大崎 由美子; 執行 聡美; 清川 真美; 宮本 剛典; 武隈 洋; 菅原 満; 井関 健, TDM研究, 25, 3, s213, s213, 2008年06月
  (一社)日本TDM学会, 日本語
• 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
  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
  (公社)日本薬剤学会, 日本語
• 化膿性脊椎炎に対するリネゾリドの臨床効果と脊椎への移行性
  加藤 貴志; 菅原 満; 井関 健; 武隈 洋; 高畑 雅彦; 小松 幹; 伊東 学; 三浪 明男, 日本薬学会年会要旨集, 128年会, 4, 85, 85, 2008年03月
  (公社)日本薬学会, 日本語
• EVALUATION OF KETOPROFEN ABSORPTION IN TWO PREPARATIONS WITH AN IN VITRO SYSTEM
  Xin He; Mitsuru Sugawara; Xingbin Zhu; Shota Kadomura; Yang Wang; Yoh Takekuma; Changxiao Liu, DRUG METABOLISM REVIEWS, 40, 31, 32, 2008年
  英語, 研究発表ペーパー・要旨（国際会議）
• 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
  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
  (一社)日本移植学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
• 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
• 01P2-154 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(薬物動態(TDM・投与設計等),医療薬学の扉は開かれた)
  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
  日本医療薬学会, 日本語
• 01P3-001 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(薬剤疫学,医療薬学の扉は開かれた)
  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
  日本医療薬学会, 日本語
• 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
  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
  (一社)日本TDM学会, 日本語
• 腎移植患者におけるタクロリムス併用時の少数採血点によるミコフェノール酸AUC0-12推定
  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
  (一社)日本TDM学会, 日本語
• 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
• 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
• 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
• 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
• 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
• Limited sampling strategy for therapeutic drug monitoring of mycophenolic acid under tacrolimus-based immunosuppression after renal transplantation.
  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
  英語, 研究発表ペーパー・要旨（国際会議）
• 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
  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
  (一社)日本TDM学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
• 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
• 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
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
• 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
• 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
• 27-02-06 循環器科病棟において TDM を有効利用した症例
  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
  日本医療薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 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
• 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
• 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
• 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
• 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
  (公社)日本薬学会, 日本語
• P-94 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
  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
  日本医療薬学会, 日本語
• 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
  (公社)日本薬学会, 日本語
• 遺伝子多型診断による副作用発現の回避システム
  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
• 13-2-D3 文書による薬剤情報提供への取り組み (2) : 「お薬手帳用ラベル」の発行と情報提供内容の公開
  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
  日本医療薬学会, 日本語
• 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

• コンパス医薬品情報学 : 理論と演習 改訂第2版
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  南江堂, 2018年12月, 9784524403592, ix, 245p, 日本語, ［分担執筆］
• 臨床現場で役立つ!実例から学ぶTDMのエッセンス
  日本TDM学会TDM実例集編集委員会; 日本TDM学会, 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, 9784840748476, 215p, 日本語, ［分担執筆］
• コンパス 医薬品情報学-理論と演習-
  武隈 洋, 7章EBMと臨床研究， B臨床研究の手法
  南江堂, 2015年09月, 日本語, ［分担執筆］
• Applied 臨床薬物動態学
  武隈 洋, 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, ［分担執筆］
• 事前実習テキスト アルティメイト
  武隈 洋, 第2章 処方せんと調剤
  京都廣川書店, 2010年04月, ［分担執筆］

• 未分画ヘパリンモニタリングにおけるAPTTと抗Xa活性の不一致に対する腎機能の影響 探索的後ろ向き観察研究
  三上 龍生; 早川 峰司; 今井 俊吾; 斉藤 智誉; 佐藤 夕紀; 柏木 仁; 梨本 俊亮; 菅原 満; 武隈 洋
  日本腎臓病薬物療法学会誌, 2025年09月, (一社)日本腎臓病薬物療法学会, 日本語
  2025年09月 - 2025年09月
• イリノテカン誘発性コリン症状に対する抗コリン薬単回予防投与の症状コントロール不良因子の探索
  渡辺 拓也; 齋藤 佳敬; 武隈 洋; 清水 康; 木下 一郎; 小松 嘉人; 菅原 満
  日本臨床腫瘍薬学会雑誌, 2025年05月, (一社)日本臨床腫瘍薬学会, 日本語
  2025年05月 - 2025年05月
• 非小細胞肺がん患者におけるドセタキセル誘発性浮腫の要因分析
  山下 慎介; 齋藤 佳敬; 今井 俊吾; 柏木 仁; 佐藤 夕紀; 梨本 俊亮; 榊原 純; 清水 康; 木下 一郎; 武隈 洋; 菅原 満
  日本臨床腫瘍薬学会雑誌, 2025年05月, (一社)日本臨床腫瘍薬学会, 日本語
  2025年05月 - 2025年05月
• アミノ酸トランスポーターSNAT4を介したエンドサイトーシスによる基質修飾リポソームの取り込み
  松山 琳空; 佐藤 夕紀; 藤田 聡; 丸山 真吾; 梨本 俊亮; 柏木 仁; 武隈 洋; 菅原 満
  日本薬剤学会年会講演要旨集, 2025年05月, (公社)日本薬剤学会, 日本語
  2025年05月 - 2025年05月
• グラム陽性球菌による骨・関節感染症に対するリネゾリドの第一選択薬としての有効性調査
  新沼 悠介; 石黒 信久; 鏡 圭介; 菅原 満; 武隈 洋
  日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集, 2025年04月, 日本感染症学会・日本化学療法学会, 日本語
  2025年04月 - 2025年04月
• TDM研究論文投稿への道に一歩踏み出そう
  武隈 洋
  TDM研究, 2024年07月, (一社)日本TDM学会, 日本語
  2024年07月 - 2024年07月
• オレキシン受容体拮抗薬のUPLC/MS/MS定量法構築とヒト乳汁移行性評価への応用
  石川 陽菜; 古堅 彩子; 西村 あや子; 馬詰 武; 青柳 亮一; 石川 修平; 鳴海 克哉; 岡本 敬介; 武隈 洋; 菅原 満; 小林 正紀
  TDM研究, 2024年07月, (一社)日本TDM学会, 日本語
  2024年07月 - 2024年07月
• ヒアルロン酸4,6,8糖の同時定量法の確立
  佐藤 夕紀; 高林 直央; 青柳 空馬; 梨本 俊亮; 柏木 仁; 武隈 洋; 菅原 満
  日本薬剤学会年会講演要旨集, 2024年05月, (公社)日本薬剤学会, 日本語
  2024年05月 - 2024年05月
• 新たなTDM対象抗菌薬の最前線 オキサゾリジノン系抗菌薬のTDM
  武隈 洋; 井上 優希; 菅原 満
  日本化学療法学会雑誌, 2024年01月, (公社)日本化学療法学会, 日本語
  2024年01月 - 2024年01月
• 食道胃接合部癌術後に食道狭窄を繰り返す症例に対して持効性注射薬カボテグラビル+リルピビリン(CAB+RPV)を導入した一例
  田澤 佑基; 遠藤 知之; 武隈 洋; 菅原 満
  日本エイズ学会誌, 2023年11月, (一社)日本エイズ学会, 日本語
  2023年11月 - 2023年11月
• 唾液サンプリングに基づくTDMの実際
  武隈 洋; 井上優希; 菅原 満
  第39回日本TDM学会・学術大会, 2023年06月24日, 日本語, シンポジウム・ワークショップパネル（公募）
  2023年06月24日 - 2023年06月25日, 34042718
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  山口 敦史; 武隈 洋; 仁木 加寿子; 平林 真介; 寺下 友佳代; 長谷河 昌孝; 長 祐子; 真部 淳; 菅原 満
  TDM研究, 2023年06月, (一社)日本TDM学会, 日本語
  2023年06月 - 2023年06月
• マスメディアによる「くすりの危険性」に関する報道に起因した患者相談の実態調査
  今井 俊吾; 阿部 真也; 松井 洸; 柏木 仁; 佐藤 夕紀; 武隈 洋; 吉町 昌子; 菅原 満
  日本医薬品情報学会総会・学術大会講演要旨集, 2023年06月, (一社)日本医薬品情報学会, 日本語
  2023年06月 - 2023年06月
• 採血に依らないTDM～Alternative samplingによるTDMに関する最新知見～ 唾液サンプリングに基づくTDMの実際
  武隈 洋; 井上 優希; 菅原 満
  TDM研究, 2023年06月, (一社)日本TDM学会, 日本語
  2023年06月 - 2023年06月
• 肝機能障害患者に対するボリコナゾールの初期投与設計におけるAlbumin-Bilirubinスコアの有用性検証
  梨本 俊亮; 今井 俊吾; 菅原 満; 武隈 洋
  TDM研究, 2023年06月, (一社)日本TDM学会, 日本語
  2023年06月 - 2023年06月
• ブスルファンの著しい薬物動態変動が認められた小児の1例
  山口 敦史; 武隈 洋; 仁木 加寿子; 平林 真介; 寺下 友佳代; 長谷河 昌孝; 長 祐子; 真部 淳; 菅原 満
  TDM研究, 2023年06月, (一社)日本TDM学会, 日本語
  2023年06月 - 2023年06月
• Cyclosporine A乳剤ならびに自己乳化型製剤の特性と経口吸収性評価
  佐藤 夕紀; 木下 祐介; 上村 聡; 丸山 真吾; 武隈 洋; 菅原 満
  日本薬剤学会年会講演要旨集, 2023年05月, (公社)日本薬剤学会, 日本語
  2023年05月 - 2023年05月
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  新沼 悠介; 鏡 圭介; 武隈 洋; 菅原 満
  日本化学療法学会雑誌, 2023年03月, (公社)日本化学療法学会, 日本語
  2023年03月 - 2023年03月
• 片頭痛の治療と予防
  武隈 洋
  令和4年度北海道医薬品卸勤務薬剤師会第２回研修会, 2023年02月15日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  ［招待講演］
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  山神彰; 鳴海克也; 鳴海克也; 齋藤佳敬; 古堅彩子; 今井俊吾; 北川善政; 大廣洋一; 高木諒; 武隈洋; 菅原満; 菅原満; 小林正紀; 小林正紀
  日本医療薬学会年会講演要旨集(Web), 2023年
  2023年 - 2023年
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  高林直央; 佐藤夕紀; 柏木仁; 梨本俊亮; 武隈洋; 菅原満; 菅原満
  バイオメディカル分析科学シンポジウム講演要旨集, 2023年
  2023年 - 2023年
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  医療薬学フォーラム講演要旨集, 2023年
  2023年 - 2023年
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  日本免疫毒性学会学術年会講演要旨集, 2023年
  2023年 - 2023年
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  青柳亮一; 窪田篤人; 窪田篤人; 今井俊吾; 今井俊吾; 八木澤啓司; 沖洋充; 山崎浩二郎; 小島弘幸; 菅原満; 菅原満; 武隈洋
  日本薬学会年会要旨集(Web), 2023年
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  日本エイズ学会誌, 2022年11月, (一社)日本エイズ学会, 日本語
  2022年11月 - 2022年11月
• 化学物質による免疫毒性:毒性発現機序と生体防御機構 炎症性腸疾患の病態制御に対する免疫学的アプローチ
  窪田 篤人; 寺崎 将; 小林 正紀; 室本 竜太; 青柳 亮一; 武隈 洋; 菅原 満; 小島 弘幸
  The Journal of Toxicological Sciences, 2022年06月, (一社)日本毒性学会, 日本語
  2022年06月 - 2022年06月
• 週刊誌に掲載された「危ないクスリ」に関する情報の整理とその適切性評価
  今井 俊吾; 柏木 仁; 佐藤 夕紀; 武隈 洋; 菅原 満
  日本医薬品情報学会総会・学術大会講演要旨集, 2022年06月, (一社)日本医薬品情報学会, 日本語
  2022年06月 - 2022年06月
• サーベイランスシステムJ-SIPHE(感染対策連携共通プラットフォーム)を用いた多施設解析-抗菌薬使用量と耐性菌の関連
  鏡 圭介; 石黒 信久; 新沼 悠介; 武隈 洋; 菅原 満
  日本化学療法学会雑誌, 2022年05月, (公社)日本化学療法学会, 日本語
  2022年05月 - 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, 2022年05月, (一社)日本TDM学会, 日本語
  2022年05月 - 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, 2022年05月, (一社)日本TDM学会, 日本語
  2022年05月 - 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, 2022年05月, (一社)日本血栓止血学会, 日本語
  2022年05月 - 2022年05月
• 重症患者におけるバンコマイシンの初期投与量決定のための実測クレアチニンクリアランスの臨床適用性
  三上 龍生; 今井 俊吾; 早川 峰司; 菅原 満; 武隈 洋
  日本薬学会年会要旨集, 2022年03月, (公社)日本薬学会, 日本語
  2022年03月 - 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, 2022年03月, (公社)日本薬学会, 日本語
  2022年03月 - 2022年03月
• 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, 2022年03月, (公社)日本薬学会, 日本語
  2022年03月 - 2022年03月
• 歯科領域における経口第3世代セフェム系抗菌薬減少戦略の評価:中断時系列分析
  山神彰; 鳴海克哉; 齋藤佳敬; 古堅彩子; 今井俊吾; 北川善政; 大廣洋一; 高木諒; 武隈洋; 菅原満; 菅原満; 小林正紀; 小林正紀
  医療薬学フォーラム講演要旨集, 2022年
  2022年 - 2022年
• リネゾリド投与患者における嘔吐発現要因の探索
  堤竹蔵; 堤竹蔵; 今井俊吾; 今井俊吾; 柏木仁; 佐藤夕紀; 菅原満; 菅原満; 菅原満; 武隈洋
  日本医療薬学会年会講演要旨集(Web), 2022年
  2022年 - 2022年
• LC/MS/MSを用いたリネゾリドならびにテジゾリドのヒト血漿中濃度同時定量法の確立
  佐藤夕紀; 大聖貴之; 柏木仁; 今井俊吾; 武隈洋; 菅原満; 菅原満
  日本医療薬学会年会講演要旨集(Web), 2022年
  2022年 - 2022年
• レセプトデータベースを用いた糖尿病患者へのオランザピンの処方実態調査
  山下慎介; 山下慎介; 今井俊吾; 今井俊吾; 百賢二; 百賢二; 柏木仁; 佐藤夕紀; 菅原満; 菅原満; 武隈洋
  日本医療薬学会年会講演要旨集(Web), 2022年
  2022年 - 2022年
• 炎症性腸疾患の病態制御に対する免疫学的アプローチ
  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, 2022年, 日本毒性学会, 日本語
  2022年 - 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。
• 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
  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, 日本語
  2021年10月 - 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, 日本語
  2021年10月 - 2021年10月
• オキシコドン徐放錠による悪心危険因子の解明と機械学習を用いたリスク推定モデルの構築
  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, 日本語
  2021年05月 - 2021年05月
• 私にもできる抗菌薬(リネゾリド)の投与設計
  武隈 洋
  TDM研究, 2021年05月, (一社)日本TDM学会, 日本語
  2021年05月 - 2021年05月
• 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
  日本薬学会第141年会, 2021年03月27日, 日本語, シンポジウム・ワークショップパネル（公募）
  2021年03月26日 - 2021年03月29日
• 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, 日本語
  2021年03月 - 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, 2021年03月, (公社)日本薬学会, 日本語
  2021年03月 - 2021年03月
• 医療の質向上、臨床の薬剤師による研究推進を目指した医療ビッグデータの活用 JMDCレセプトデータベースを用いた臨床研究
  武隈 洋; 今井 俊吾; 菅原 満
  日本薬学会年会要旨集, 2021年03月, (公社)日本薬学会, 日本語
  2021年03月 - 2021年03月
• 日本におけるコルヒチンと強力なCYP3A4阻害薬/P糖蛋白質阻害薬の併用実態の解明
  今井 俊吾; 百 賢二; 柏木 仁; 宮井 貴之; 菅原 満; 武隈 洋
  日本腎臓病薬物療法学会誌, 2020年11月, 日本腎臓病薬物療法学会, 日本語
  2020年11月 - 2020年11月
• ASTによるカルバペネム系抗菌薬および抗MRSA薬のdaily reviewが抗菌薬使用量および患者アウトカムに与える影響
  鏡 圭介; 石黒 信久; 山田 武宏; 新沼 悠介; 武隈 洋; 菅原 満; 小山田 玲子; 渡邊 翼; 早坂 かすみ; 福元 達也; 岩崎 澄央; 瀧 圭介
  日本化学療法学会雑誌, 2020年09月, (公社)日本化学療法学会, 日本語
  2020年09月 - 2020年09月
• 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, 日本語
  2020年03月 - 2020年03月
• 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, 日本語
  2020年03月 - 2020年03月
• 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, 日本語
  2020年03月 - 2020年03月
• BCR-ABLチロシンキナーゼ阻害剤(TKI)の一時的曝露による持続的細胞増殖抑制効果の検討
  青山 剛; 武隈 洋; 今井 俊吾; 柏木 仁; 菅原 満
  日本薬学会年会要旨集, 2020年03月, (公社)日本薬学会, 日本語
  2020年03月 - 2020年03月
• 院内製造18F-FDGのエンドトキシン試験における反応干渉因子に関する検討
  小林 准; 西嶋 剣一; 大曲 茂生; 山崎 純一; 菊池 康子; 久下 裕司; 武隈 洋; 菅原 満
  日本薬学会年会要旨集, 2020年03月, (公社)日本薬学会, 日本語
  2020年03月 - 2020年03月
• Improvement of renal function estimation equations for elderly Japanese people
  武隈 洋
  The 5th Japan-Taiwan Joint Symposium for Pharmaceutical Sciences, 2019年08月30日, 英語, 口頭発表（招待・特別）
  2019年08月30日 - 2019年08月30日, ［招待講演］
• 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
  武隈 洋
  医療薬学フォーラム2019/ 第27回クリニカルファーマシーシンポジウム, 2019年07月13日, 日本語, シンポジウム・ワークショップパネル（指名）
  ［国内会議］
• 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
  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, 日本語, 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
  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, 日本語, 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
  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, 日本語, 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
  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, 日本語, 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
  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, 日本語, 口頭発表（一般）
• 加齢による薬物動態の変化について
  武隈 洋
  第9回 札幌薬剤師会 臨床薬学講演会, 2018年09月13日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  ［招待講演］, ［国内会議］
• 消化管活動性がニロチニブの吸収性に及ぼす影響
  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23日, 日本語, ポスター発表
  ［国内会議］
• 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
  日本薬剤学会第33年会, 2018年05月30日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  日本薬学会第138年会, 2018年03月25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  日本薬学会第138年会, 2018年03月25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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; 上野博文; 菅原 満; 武隈 洋
  日本薬学会第138年会, 2018年03月25日, 日本語, ポスター発表
  ［国内会議］
• 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
  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, 日本語, 口頭発表（一般）
• Emulsification using oxa acids for oral administration and the improvement of intestinal absorption of Coenzyme Q10
  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09日, 英語, ポスター発表
  ［国際会議］
• パゾパニブの投与量と投与継続期間の後ろ向き調査
  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03日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  第50回日本薬剤師会学術大会, 2017年10月08日, 日本語, ポスター発表
  ［国内会議］
• Continuous cytostatic effects of BCR-ABL tyrosine kinase inhibitors (TKIs) after washout in human leukemic K562 cells
  Tsuyoshi Aoyama; Yoh Takekuma; Masato Sumi; Yuki Sato; Mitsuru Sugawara
  15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT), 2017年09月24日, 英語, ポスター発表
  ［国際会議］
• パゾパニブの血中濃度に影響する因子の検討
  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23日, 日本語, ポスター発表
  ［国内会議］
• パゾパニブの血中濃度に影響する因子の探索
  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, 日本語
• 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
  日本薬学会第137年会, 2017年03月25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  日本薬学会第137年会, 2017年03月25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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, 日本語
• 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
  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17日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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14日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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33回日本TDM学会・学術大会, 2016年05月28日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  日本薬剤学会第31年会, 2016年05月19日, 日本語, 口頭発表（一般）
  ［国内会議］
• 脂質異常症治療薬エゼチミブ によるα-トコフェロールの消化管 吸収抑制とその回避策
  梨本俊亮; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満
  日本薬学会第136年会, 2016年03月28日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  第16回日本医薬品情報学会総会・学術大会, 2015年06月27日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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26日, 日本語, ポスター発表
  ［国内会議］
• 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
  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23日, 日本語, ポスター発表
  ［国内会議］
• 高度腎機能障害および透析時のリネゾリド投与量設計
  武隈 洋
  第32回日本TDM学会・学術大会（松本）, 2015年05月23日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  ［招待講演］, ［国内会議］
• 乳剤化によるコエンザイムQ10 の消化管吸収改善
  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21日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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
  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21日, 日本語, 口頭発表（一般）
  ［国内会議］
• Niemann-Pick C1 Like-1 (NPC1L1) を標的とした乳剤化による難吸収性物質の吸収改善
  竹川悠人; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満
  日本薬学会第135年会, 2015年03月25日, 日本語, 口頭発表（一般）
  ［国内会議］
• 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～
  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27日
  ［国内会議］
• 臨床応用を目指したHPLC-UV法による血中imatinib定量法の確立
  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31日
  ［国内会議］
• 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～
  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21日
  ［国内会議］
• 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
  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10日
  ［国内会議］
• Intracellular uptake mechanism of lutein in retinal pigment epithelial cells
  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24日, ポスター発表
  ［国際会議］
• 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
  日本薬剤学会年会第28年会（名古屋）, 2013年05月23日
  ［国内会議］
• 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
  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27日
  ［国内会議］
• 一包化調剤時におけるスタチン製剤の保存安定性
  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27日
  ［国内会議］
• 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
  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28日
  ［国内会議］
• IMPROVEMENT OF INTESTINAL ABSORPTION OF FUNCTIONAL FOODS, LUTEIN AND COENZYME Q10
  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19日
  ［国際会議］
• 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
  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24日
  ［国内会議］
• 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
  第9回日本機能性食品医用学会総会（大阪）, 2011年12月10日
  ［国内会議］
• 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
  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09日
  ［国内会議］
• 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～
  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18日
  ［国内会議］
• 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
  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28日
  ［国内会議］
• テアニンの消化管吸収に関与するトランスポーター
  川守田渉; 堀田雄也; 佐藤夕紀; 鷲見正人; 武隈 洋; 菅原 満
  日本薬学会第131年会（静岡）, 2011年03月28日
  ［国内会議］
• 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
  日本薬学会第131年会（静岡）, 2011年03月28日
  ［国内会議］
• 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
  日本薬剤学会第25年会（徳島）, 2010年05月12日
  ［国内会議］
• PK/PD概念に基づいた抗がん剤の分類
  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28日
  ［国内会議］
• 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
  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28日
  ［国内会議］
• 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
  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28日
  ［国内会議］
• 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
  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13日
  ［国内会議］
• 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
  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13日
  ［国内会議］
• テイコプラニン初期投与設計への薬剤師介入の効果
  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13日
  ［国内会議］
• Intestinal absorption of emulsified preparation of drugs belong to BCS class 4
  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16日, ポスター発表
  ［国際会議］
• 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
  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30日
  ［国内会議］
• 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
  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23日
  ［国内会議］
• 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
  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20日
  ［国内会議］
• 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
  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20日
  ［国内会議］
• 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
  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21日
  ［国内会議］
• 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
  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20日
  ［国内会議］
• 20E-03 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(後発医薬品,来るべき時代への道を拓く)
  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, 2008年, 一般社団法人 日本医療薬学会, 日本語
  2008年 - 2008年
• 20C-18 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(感染対策・ICT,来るべき時代への道を拓く)
  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, 2008年, 一般社団法人 日本医療薬学会, 日本語
  2008年 - 2008年
• 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
  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
  ［国内会議］
• 化膿性脊椎炎に対するリネゾリドの臨床効果と脊椎への移行性
  加藤貴志; 菅原 満; 井関 健; 武隈 洋; 高畑雅彦; 小松幹; 伊東 学; 三浪明男
  日本薬学会第128年会（横浜）, 2008年
  ［国内会議］
• 29-P1-143 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(TDM/薬物動態,社会の期待に応える医療薬学を)
  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, 2007年, 一般社団法人 日本医療薬学会, 日本語
  2007年 - 2007年
• 29-P1-134 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(TDM/薬物動態,社会の期待に応える医療薬学を)
  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, 2007年, 一般社団法人 日本医療薬学会, 日本語
  2007年 - 2007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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• Cooperation of concentrative nucleoside transporter (CNT) and equilibrative nucleoside transporter (ENT) in the uptake of ribavirin
  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
  ［国内会議］
• 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～
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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; 井関 健
  日本薬剤学会第21年会（金沢）, 2006年
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  日本薬学会第125年会（東京）, 2005年
  ［国内会議］
• 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
  ［国内会議］
• LIMITED SAMPLING STRATEGY FOR THERAPEUTIC DRUG MONITORING OF MYCOPHENOLIC ACID AFTER RENAL TRANSPLANTATION
  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08日
  ［国際会議］
• Regulatorymechanisms of ATA2(SNAT2), an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock, and amino acid deprivation
  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
  ［国内会議］
• Structure-affinity relationship in the interactions of human organic anion transporter 1 with nucleic acids and their analogs
  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
  ［国内会議］
• 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-
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• Inhibitory effects of basic drugs on the sodium-dependent transport of L-alanine via system B0 in the small intestine
  Mitsuru Sugawara; Mayumi Kitakubo; Yoh Takekuma; Vadivel Ganapathy; Katsumi Miyazaki
  Pharmaceutical Sciences World Congress（Kyoto）, 2004年
  ［国際会議］
• Transport of ribavirin via nucleoside transporters in the trophoblast
  Takashi Morita; Yoh Takekuma; Mitsuru Sugawara; Katsumi Miyazaki
  Pharmaceutical Sciences World Congress（Kyoto）, 2004年
  ［国際会議］
• 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
  日本薬学会第124年会（大阪）, 2004年
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  日本薬学会第124年会（大阪）, 2004年
  ［国内会議］
• 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
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 循環器科病棟においてTDMを有効利用した症例
  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
  ［国内会議］
• 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〜
  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
  ［国内会議］
• 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; Vadivel ganapathy; 宮崎勝巳
  日本薬学会第123年会（長崎）, 2003年
  ［国内会議］
• 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
  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
  ［国内会議］
• 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; 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
  ［国内会議］
• 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−
  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
  ［国内会議］
• 遺伝子多型診断による副作用発現の回避システム
  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
  ［国内会議］
• 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
  日本薬学会第121年会（札幌）, 2001年
  ［国内会議］
• 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
  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
  ［国内会議］
• 生体肝移植患者におけるタクロリムスの体内動態
  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
  ［国内会議］
• 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
  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
  ［国内会議］
• 文書による薬剤情報提供への取り組み
  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
  ［国内会議］
• 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〜
  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
  ［国内会議］
• 薬物の生体内動態における構造相関（第40報）−物理化学的測定値を用いた薬物の消化管吸収予測式の構築−
  菅原 満; 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
  ［国内会議］
• 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
  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）
  ［国内会議］
• 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−
  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
  ［国内会議］

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• 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

• 唾液中薬物濃度モニタリングが適用可能な薬物の選択方法の確立
  科学研究費助成事業
  2024年04月01日 - 2027年03月31日
  武隈 洋; 佐藤 夕紀; 柏木 仁
  日本学術振興会, 基盤研究(C), 北海道大学, 24K09933
• 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
  科学研究費助成事業 基盤研究(C)
  2021年04月 - 2024年03月
  武隈 洋; 佐藤 夕紀; 今井 俊吾
  今年度は、リネゾリド（LZD）およびテジゾリド（TZD）の血中濃度モニタリングの代替指標として唾液中濃度が利用できるかを検証するための準備として、ラットを用いて唾液中への薬物移行性を評価する系の確立に着手した。ラットをウレタン麻酔した状態で、顕微鏡下で顎下腺の口腔内開口部へカニュレーションを施した。定量に十分な唾液量を採取するために、既報（Nezu A. et al., Exp. Physiol., 104, 61-69 (2019)）を参考にアセチルコリンを大腿静脈へ施したカニュレーションからシリンジポンプを用いて投与した。投与速度と唾液の分泌量を評価したところ、260 nmol/minでアセチルコリンを投与すると10分間で200μL以上唾液を採取可能であった。
  並行して、母集団薬物動態から乖離する患者の要因の抽出を検証するために共同研究者が入手したリアルワールドデータ株式会社が提供する電子カルテ由来の診療情報データベースを用いた解析を行った。対象薬剤は特定薬剤治療管理料１の対象ではないため一般に血中濃度モニタリングは実施されていない。そのため、血中濃度データは格納されていないので、LZD血中濃度と発症率の相関が報告されている血小板減少症を代替指標として、血小板減少症の発症リスクを1,399症例を対象として解析した。その結果、LZDの14日以上の長期投与、体重45kg未満、eGFR 30mL/min/1.73m2がリスク因子として抽出された。特に医療ビッグデータを利用することで症例が多く確保できたので、既報では解析できなかったeGFRの層別解析が可能となり、LZDが7日未満の投与であっても、eGFR 15mL/min/1.73m2でリスクが上昇することを明らかにした。
  日本学術振興会, 基盤研究(C), 北海道大学, 21K06684
• 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
  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
  2016年04月 - 2019年03月
  菅原 満
  日本学術振興会, 競争的資金
• 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
  長寿科学研究者支援事業
  2017年06月 - 2018年03月
  武隈 洋
  公益財団法人長寿科学振興財団, 研究代表者, 競争的資金
• 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
  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
  2013年04月 - 2016年03月
  菅原 満
  日本学術振興会, 競争的資金
• 抗がん剤併用療法時の薬物暴露順序の影響
  研究奨励金
  2012年04月 - 2014年03月
  武隈 洋
  臨床薬理研究振興財団, 研究代表者, 競争的資金
• 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
  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)
  2012年04月 - 2014年03月
  武隈 洋
  日本学術振興会, 研究代表者, 競争的資金
• 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
  研究助成
  2010年04月 - 2011年03月
  武隈 洋
  栗林育英学術財団, 研究代表者, 競争的資金
• 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
  奨励助成
  2006年04月 - 2007年03月
  武隈 洋
  秋山記念生命科学振興財団, 研究代表者, 競争的資金
• 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
  科学研究費補助金（奨励研究）
  2004年04月 - 2005年03月
  武隈 洋
  日本学術振興会, 奨励研究, 北海道大学病院, 研究代表者, 競争的資金, 16922077

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

• 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
  2009年08月19日
  講師
  北海道医療大学