Akiyoshi, Takeshi



Faculty of Pharmacy, Department of Pharmacy 臨床薬物動態学講座 (Shiba-Kyoritsu)


Assistant Professor/Senior Assistant Professor

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Books 【 Display / hide

  • 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, 2018.01

    Scope: 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

    Scope: 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, 2012.01

    Scope: 80-129

Papers 【 Display / hide

  • pH-Dependent transport kinetics of human organic anion transporting polypeptide 1A2.

    Morita T, Akiyoshi T, Sato R, Katayama K, Yajima K, Kataoka H, Imaoka A, Sugimoto Y, Ohtani H.

    Drug Metabol Pharmacokinet   2020

    Research paper (scientific journal), Joint Work, Accepted

  • Irinotecan-induced gastrointestinal damage impairs the absorption of dabigatran etexilate.

    Hattori T, Imaoka A, Akiyoshi T, Ohtani H

    Biopharmaceutics & drug disposition (Biopharmaceutics and Drug Disposition)  40 ( 9 ) 315 - 324 2019.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0142-2782

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    © 2019 John Wiley & Sons, Ltd. Irinotecan causes serious gastrointestinal damage. Dabigatran etexilate (DABE), an oral anticoagulant and substrate of P-glycoprotein (P-gp), is poorly absorbed and exhibits low bioavailability in humans. The aim of this study was to evaluate the effects of irinotecan-induced gastrointestinal damage on the pharmacokinetics/pharmacodynamics (PK/PD) of DABE. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. To investigate the PK profile of dabigatran (DAB), an active moiety of DABE, DABE was administered orally on day 5, and then DAB was administered intravenously on day 6. To evaluate the PD profile of DAB, the activated partial thromboplastin time (APTT) was measured. The protein expression level of intestinal P-gp was evaluated. In the irinotecan-treated rats, the area under the concentration–time curve of DAB after the oral administration of DABE and the bioavailability of DABE were decreased significantly. The APTT ratio also decreased, suggesting that the impaired efficacy of DABE was attributable to a reduction in its bioavailability. The expression of intestinal P-gp was higher in the irinotecan-treated rats. Taking into consideration the histological damage caused to the intestinal epithelium, both the increased P-gp expression and the reduced passive diffusion were considered to be responsible for the reduction in the bioavailability of DABE.

  • インターネットオークションにおける無承認無許可医薬品の出品実態.

    大谷壽一*, 藤井萌未, 今岡鮎子, 秋好健志.

    医療薬学 45 ( 10 ) 591 - 595 2019.10

    Research paper (scientific journal), Joint Work, Accepted

  • Inhibitory kinetics of fruit components on CYP2C19 activity.

    Seki H, AKIYOSHI Takeshi, Imaoka A, Ohtani H.

    Drug Metabol Pharmacokinet (Drug Metabolism and Pharmacokinetics)  34 ( 3 ) 181 - 186 2019

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13474367

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    © 2019 The Japanese Society for the Study of Xenobiotics It has been suggested that the fruit components resveratrol (RSV), 6′, 7′-dihydroxybergamottin (DHB), and bergamottin (BG) might inhibit cytochrome P450 2C19 (CYP2C19) activity, but the mode and potency of such inhibition are yet to be investigated. This study aimed to investigate the mode and kinetics of the inhibition of CYP2C19-based omeprazole metabolism by RSV or grapefruit juice components (DHB or BG). RSV and DHB reduced CYP2C19 activity in a preincubation time-dependent manner, suggesting that they inactivated CYP2C19 via mechanism-based inhibition (MBI). Although BG inactivated CYP2C19 in a preincubation time- and concentration-dependent manner, suggesting that both MBI and reversible inhibition contributed to these effects, the concentration required to achieve 50% inhibition was 26-fold higher for reversible inhibition than for MBI (0.859 and 0.0331 μM, respectively), indicating that the inhibition of CYP2C19 by BG is primarily attributable to MBI. Based on the estimated intestinal concentrations of these components, it is considered that >90% of CYP2C19 would be inactivated after the consumption of normal amounts of grapefruit juice or RSV-containing substances. In conclusion, these findings suggest that food containing these components has the potential to evoke drug-food interactions caused by the MBI of intestinal CYP2C19 activity in the clinical setting.

  • Effects of food type on the extent of drug-drug interactions between activated charcoal and phenobarbital in rats

    Ogata Y., Imaoka A., Akiyoshi T., Ohtani H.

    Drug Metabolism and Pharmacokinetics (Drug Metabolism and Pharmacokinetics)  34 ( 4 ) 287 - 291 2019

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13474367

     View Summary

    © 2019 Activated charcoal is known to decrease the intestinal absorption of co-administered drug by adsorption. The extent of this drug-drug interaction (DDI) is attenuated by food intake. The aim of this study was to quantitatively evaluate the effects of food type on the extent of DDI between phenobarbital and activated charcoal using a rat model. Phenobarbital was orally administered at a dose of 1.5 mg/kg with or without 33 mg/kg of activated charcoal under fasted or fed conditions, and the plasma concentration profile of phenobarbital was monitored. Several fed conditions, such as a standard breakfast, high-fat meal or enteral nutrient used in human studies, were examined. Under the fasted conditions, activated charcoal significantly decreased the area under the plasma concentration - time curve (AUC) of phenobarbital by 45.2%. When the standard breakfast or high-fat meal was fed, this DDI was reduced to 28.3 and 18.0%, respectively, as assessed by the reduction in the AUC. On the contrary, enteral nutrient did not significantly attenuate the DDI. In conclusion, the influence of food intake on the extent of DDI between phenobarbital and activated charcoal was found to differ among the types of food concomitantly ingested.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 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

    AKIYOSHI Takeshi

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

    Introduction and explanation (commerce magazine), Single Work

  • 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

    AKIYOSHI Takeshi

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

    Introduction and explanation (commerce magazine)

Presentations 【 Display / hide

  • 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) , 2020.03, Poster (general), 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) , 2020.03, Poster (general), 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, 2019.12, Oral Presentation(general)

  • 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) , 2019.10, Poster (general), 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) , 2019.07, Poster (general), Asian Association of Schools of Pharmacy

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 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~


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 秋好 健志, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 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~


    文部科学省, 科学研究費, 秋好健志, 基盤研究 (C), Research grant

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


    薬学研究奨励財団, 薬学研究奨励財団 研究助成金, Takeshi Akiyoshi, Research grant, Principal Investigator

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


    一般財団法人横山臨床薬理研究助成基金, 研究助成金, Takeshi Akiyoshi, Research grant, Principal Investigator

  • 抗がん剤併用時の薬物吸収とIVIVEに関する研究


    日本学術振興会, Grant-in-Aid for Scientific Research, Takeshi Akiyoshi, Research grant, Principal Investigator

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Awards 【 Display / hide

  • 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. , 2018.09, 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.

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 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, 2017.09, 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

    Country: 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., 2017.07, 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., 2017.06, 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., 2017.06, 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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Courses Taught 【 Display / hide











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