秋好　健志 (アキヨシ　タケシ)

Akiyoshi, Takeshi

写真a

所属（所属キャンパス）

薬学部 薬学科 臨床薬物動態学講座 （芝共立）

職名

専任講師
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  • MRテキスト2018, 医薬品情報.

    大谷壽一(編), 大谷壽一, 秋好健志., 南山堂, 東京, 2018年01月

    担当範囲: 16-38

  • MRテキストI, 医薬品情報2012. 2015改訂

    大谷壽一, 岡淳一郎, 折井孝男(編), 大谷壽一, 秋好健志, 他執筆., 南山堂, 東京, 2015年

    担当範囲: 80-109

  • MRテキストI, 医薬品情報2012.

    大谷壽一, 岡淳一郎, 折井孝男(編), 大谷壽一, 秋好健志, 他執筆., 南山堂, 東京, 2012年01月

    担当範囲: 80-129

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  • Exacerbation of atrioventricular block associated with concomitant use of amlodipine and aprepitant in a lung cancer patient: A case report.

    Hibino H, Makino Y, Sakiyama N, Makihara-Ando R, Hashimoto H, Akiyoshi T, Imaoka A, Fujiwara Y, Ohe Y, Yamaguchi M, Ohtani H

    International journal of clinical pharmacology and therapeutics （International Journal of Clinical Pharmacology and Therapeutics)  In press （ 4 ） 328 - 332 2020年12月

    研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0946-1965

    　概要を見る

    Objective: To report a case of second-degree atrioventricular block associated with concomitant use of aprepitant and amlodipine. Case: A 73-year-old man with lung cancer was treated with aprepitant for prophylactic use for the prevention of nausea and vomiting, concomitantly with cisplatin, gemcitabine, and an investigational drug (anti-epidermal growth factor receptor monoclonal antibody). He was diagnosed with first-degree atrioventricular block and was taking amlodipine for hypertension. During the first cycle of chemotherapy, 5 days after the start of aprepitant, he experienced Wenckebach second-degree atrioventricular block (Mobitz type I), and amlodipine was discontinued. After day 6, the atrioventricular block was not shown. According to the Naranjo adverse drug reaction scale, a score of 7 was obtained (causality: probable). In addition, using the Drug Interaction Probability Scale, a score of 6 was obtained (causality: probable). Conclusion: The drug-drug interaction between aprepitant and amlodipine was considered to have deteriorated his atrioventricular block, conceivably due to the inhibition of cytochrome P450 (CYP) 3A-mediated metabolism of amlodipine by aprepitant.

  • Citrus Fruit-Derived Flavanone Glycoside Narirutin is a Novel Potent Inhibitor of Organic Anion-Transporting Polypeptides.

    Morita T, Akiyoshi T, Sato R, Uekusa Y, Katayama K, Yajima K, Imaoka A, Sugimoto Y, Kiuchi F, Ohtani H

    Journal of agricultural and food chemistry （Journal of Agricultural and Food Chemistry)  68 （ 48 ） 14182 - 14191 2020年11月

    研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0021-8561

    　概要を見る

    © 2020 American Chemical Society. All rights reserved. Organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1 are expressed in the small intestine and are involved in drug absorption. We identified narirutin, which is present in grapefruit juice, as a novel OATP inhibitor. The citrus fruit jabara also contains high levels of narirutin; therefore, we investigated the inhibitory potency of jabara juice against OATPs. The inhibitory effects of various related compounds on the transport activity of OATPs were evaluated using OATP-expressing HEK293 cells. The IC50 values of narirutin for OATP1A2- and OATP2B1-mediated transport were 22.6 and 18.2 μM, respectively. Other flavanone derivatives from grapefruit juice also inhibited OATP1A2/OATP2B1-mediated transport (order of inhibitory potency: naringenin > narirutin > naringin). Five percent jabara juice significantly inhibited OATP1A2- and OATP2B1-mediated transport by 67 ± 11 and 81 ± 5.5%, respectively (p < 0.05). Based on their inhibitory potency and levels in grapefruit juice, the inhibition of OATPs by grapefruit juice is attributable to both naringin and narirutin. Citrus × jabara, which contains narirutin, potently inhibits OATP-mediated transport.

  • Relative contributions of metabolic enzymes to systemic elimination can be estimated from clinical DDI studies: Validation using an in silico approach.

    Koinuma K, Tsuchitani T, Imaoka A, Akiyoshi T, Ohtani H

    International journal of clinical pharmacology and therapeutics （International Journal of Clinical Pharmacology and Therapeutics)  In press （ 3 ） 231 - 238 2020年11月

    研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0946-1965

    　概要を見る

    Objective: The contribution ratios (CR) of metabolic enzymes to the systemic clearance of a drug can be estimated from in vitro studies. Another feasible approach is to calculate them based on the increase in the area under the time-concentration curve (AUC) caused by the co-administration of a potent and selective inhibitor in a clinical drug-drug interaction (DDI) study. However, some factors, such as the inhibitory potency of the inhibitor and the inhibition of first-pass metabolism, might affect the estimation of CR based on clinical DDI studies. We aimed to validate the accuracy of the DDI-based estimation of CR using an in silico approach. Materials and methods: An in silico DDI study was conducted using a population-based physiological pharmacokinetic simulator to estimate the CR of cytochrome P450 (CYP)3A4 for zolpidem, sildenafil, omeprazole, triazolam, and repaglinide. The ratio of the AUC value seen in the presence of an inhibitor (ketoconazole or itraconazole) to that observed in the absence of the inhibitor (AUC ratio) was also calculated. The CR for CYP3A4 obtained using the simulator (CR ) were compared with those calculated from the AUC ratio (CR ). Results: When ketoconazole was used, good correlations between the CR and CR were obtained for all examined substrates (inconsistencies were seen in < 10% of subjects). CR estimates derived from the AUC ratio were found to be accurate. Some underestimation was observed, possibly due to incomplete inhibition, and some overestimation caused by extensive first-pass metabolism was noted. Conclusion: This study verified that CR obtained from AUC ratios in DDI studies are quite reliable. def est est def

  • Novel method to estimate the appropriate dosing interval for activated charcoal to avoid interaction with other drugs.

    Ohtani H, Nakamura K, Imaoka A, Akiyoshi T

    European journal of clinical pharmacology （European Journal of Clinical Pharmacology)  76 （ 11 ） 1529 - 1536 2020年09月

    研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0031-6970

    　概要を見る

    © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Activated charcoal is known to adsorb a variety of drugs concomitantly administered and reduce their intestinal absorption, and separating the dosing is considered a practical approach to avoid this drug interaction. The aim of the present study was to develop and validate a simple method to estimate the sufficient dosing interval to avoid drug interaction using the pharmacokinetic profile of the subject drugs administered alone and the amplitude of interaction upon simultaneous administration with activated charcoal. Methods: For each subject drug, the pharmacokinetic profile and the amplitude of interaction, as assessed by AUCR (the ratio of area under the plasma concentration-time curve (AUC) in the presence of activated charcoal to that in its absence), were collected from previous reports. The AUCR value was estimated based on the compartment model under the assumption that the subject drug in the first gastrointestinal compartment is immediately adsorbed to a certain extent upon the administration of activated charcoal. The estimated AUCR (AUCRe) for each drug with certain dosing interval was compared with the respective AUCR value reported previously (AUCRobs). Results: Among twenty concentration profiles for 14 subject drugs obtained from previous reports, 15 AUCRe values fell in the range of 80–120% of the respective AUCRobs values. Conclusion: The developed method enabled estimation of the amplitude of DDI by activated charcoal administered in a certain dosing interval, whereas overestimation of AUCRe was observed for drugs that undergo extensive enterohepatic circulation.

  • Profile of the inhibitory effects of gefitinib on CYP2D6 variants in vitro.

    Semba Y, Akiyoshi T, Hibino H, Imaoka A, Ohtani H

    International journal of clinical pharmacology and therapeutics （International journal of clinical pharmacology and therapeutics)  58 （ 10 ） 539 - 542 2020年07月

    研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0946-1965

    　概要を見る

    OBJECTIVE: CYP2D6 is a highly polymorphic metabolic enzyme with more than 100 genetic variants, some of which are associated with significantly altered enzyme activity, such as CYP2D6.2 (Arg296Cys, Ser486Thr), CYP2D6.10 (Pro34Ser, Ser486Thr), and CYP2D6.39 (Ser486Thr). Gefitinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) and is used to treat non-small-cell lung cancer with EGFR mutations. Gefitinib is known to competitively inhibit CYP2D6 activity. The aim of this study was to quantitatively compare the inhibitory effects of gefitinib on CYP2D6 enzyme kinetics among CYP2D6 variants. MATERIALS AND METHODS: The enzymatic activity of several CYP2D6 genetic variants; i.e., CYP2D6.1 (wild type), CYP2D6.2, CYP2D6.10, and CYP2D6.39, was assessed by examining the O-demethylation of dextromethorphan. RESULTS AND CONCLUSION: The intrinsic clearance of dextromethorphan (Vmax/Km) for CYP2D6.2, CYP2D6.10, and CYP2D6.39 were 0.565-, 0.0376-, and 0.470-fold of that for wild type, respectively. For all variants, the mixed inhibition model was better at explaining the nature of the inhibitory effects of gefitinib than the competitive inhibition model. However, the inhibitory potency of gefitinib varied among the CYP2D6 genetic variants. The Ki values for CYP2D6.2, CYP2D6.10, and CYP2D6.39 were 1.4-, 2.5- and 1.5-fold higher than that for wild type, respectively, implying that these variants are less susceptible to the inhibition by gefitinib. The genetic variations in CYP2D6 might be one of the factors responsible for inter-individual differences in the strength of CYP2D6-mediated drug interactions involving gefitinib.

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  • Epstein-Barr-Virus 感染癌細胞における microRNA を介した癌転移機構の解明

    秋好 健志

    Annual Report of YOKOYAMA Foundation for Clinical Pharmacy 25   58 - 60 2017年

    総説・解説（商業誌、新聞、ウェブメディア）, 単著

  • P450を介した薬物相互作用に個人差をもたらす遺伝的要因の定量的解明と予測

    秋好 健志 大谷壽一 今岡鮎子

    臨床薬理の進歩 (臨床薬理研究振興財団)     128 - 129 2016年

    総説・解説（商業誌、新聞、ウェブメディア）

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  • CYP2C9 遺伝的変異型における resveratrol および sesamin の阻害特性の比較

    稲田理乃, 秋好健志, 今岡鮎子, 大谷壽一.

    日本薬学会第 140 年会 (京都) , 2020年03月, ポスター（一般）, 日本薬学会

  • CYP2C19 変異型分子種の代謝活性に及ぼす温度の影響.

    趙澄江, 秋好健志, 渡辺大智, 関　博行, 今岡鮎子, 山崎浩史, 下地みゆき, 中村克徳, 大谷壽一.

    日本薬学会第 140 年会 (京都) , 2020年03月, ポスター（一般）, 日本薬学会

  • High and low affinity kinetics of OATP2B1 - Inhibitory potency and pH-dependency of inhibitors

    佐藤 稜, 秋好健志, 今岡鮎子, 植草義徳, 木内文之, 片山和浩, 杉本芳一, 大谷壽一.

    日本薬物動態学会　第 34 年会, 2019年12月, 口頭（一般）

  • Identification and characterization of a novel OATP2B1 inhibitor from citrus fruits juice

    森田時生, 秋好健志, 矢島広大, 今岡鮎子, 片山和浩, 杉本芳一, 大谷壽一.

    第 13 回 次世代を担う若手医療薬科学シンポジウム. (岐阜) , 2019年10月, ポスター（一般）, 日本薬学会医療薬科学部会

  • Comparative analysis of CYP2C19 enzyme kinetics among six genetic variants.

    Watanabe D, Shimoji M, Seki H, Akiyoshi T, Imaoka A, Murakami A, Kishimoto H, Murayama N, Yamazaki H, Nakamura K, Ohtani H.

    Asian Association of Schools of Pharmacy Conference. (Suwon, Korea) , 2019年07月, ポスター（一般）, Asian Association of Schools of Pharmacy

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競争的資金等の研究課題 【 表示 ／ 非表示 】

  • フェキソフェナジンと各種柑橘類の消化管吸収過程における相互作用リスクの評価

    2020年06月
    -
    2021年03月

    公益財団法人　一般用医薬品セルフメディケーション振興財団, 令和2年度調査・研究助成金, 秋好健志, 補助金,  代表

  • 標的絶対定量プロテオーム解析を用いた抗がん剤曝露下での薬物輸送担体発現変動解明

    2020年04月
    -
    2021年03月

    中冨健康科学振興財団, 第３２回中冨健康科学振興財団 「研究助成金」, 秋好健志, 補助金,  代表

  • 抗がん剤による薬物トランスポーターの発現変動～メカニズムと薬物体内動態への影響～

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 秋好　健志, 基盤研究（Ｃ）, 補助金,  代表

  • Epstein-Barr-Virus感染癌細胞におけるmicroRNAを介した転移機構の解明

    2017年04月
    -
    2019年03月

    薬学研究奨励財団, 薬学研究奨励財団　研究助成金, 秋好健志, 補助金,  代表

  • Epstein-Barr-Virus感染癌細胞におけるmicroRNAを介した転移機構の解明

    2016年11月
    -
    2017年10月

    一般財団法人横山臨床薬理研究助成基金, 研究助成金, 秋好健志, 補助金,  代表

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受賞 【 表示 ／ 非表示 】

  • 優秀ポスター発表賞

    森田時生，佐藤稜，秋好健志, 今岡鮎子, 片山和浩, 杉本芳一, 大谷壽一. , 2018年09月, 第62回日本薬学会関東支部会, ヒト小腸有機アニオン輸送ポリペプチド OATP1A2 および OATP2B1 の pH sensitive な輸送特性の解析.

    受賞区分： 国内学会・会議・シンポジウム等の賞,  受賞国： 日本

  • 優秀口演発表賞

    土谷聡耀, 今岡鮎子, 秋好健志, 大谷壽一, 2017年09月, 第61回日本薬学会関東支部大会, イリノテカンによる消化管障害がジゴキシンの吸収に与える影響

    受賞国： 東京

  • 学生優秀発表賞

    ○中村 幸大,　今岡 鮎子,　秋好 健志,　大谷 壽一,　慶應大・薬., 2017年07月, 第20回日本医薬品情報学会総会・学術大会, 医薬品と活性炭との相互作用の回避のための投与設計法の構築と評価

  • 優秀発表賞

    ○今岡 鮎子, 関 耕平, 秋好 健志, 大谷 壽一., 2017年06月, 日本医療薬学会「第1回フレッシャーズ・カンファランス」, 薬物吸収に対する胃内 pH および食事の影響 －小動物を用いた評価－

  • 優秀発表賞

    ○四元 敬一, 今岡 鮎子, 秋好 健志, 大谷 壽一., 2017年06月, 日本医療薬学会「第1回フレッシャーズ・カンファランス」, 5-FU誘発性消化管障害時のジゴキシンの吸収変動

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担当授業科目 【 表示 ／ 非表示 】

  • Ｔｈａｉ　Ｐｈａｒｍａｃｙ　Ｅｘｐｅｒｉｅｎｃｅ

    2021年度

  • 課題研究（臨床薬物動態学）

    2021年度

  • 演習（臨床薬物動態学）

    2021年度

  • 卒業研究１（薬学科）

    2021年度

  • 実務実習事前学習２

    2021年度

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