Akiyoshi, Takeshi



Faculty of Pharmacy, Department of Pharmacy Department of Clinical pharmacokinetics (Shiba-Kyoritsu)


Assistant Professor/Senior Assistant Professor

Profile Summary 【 Display / hide

Academic Degrees 【 Display / hide

  • Ph.D.(Pharmacy), Fukuoka University, Dissertation, 2008.03

Licenses and Qualifications 【 Display / hide

  • 薬剤師, 2001.05


Research Areas 【 Display / hide

  • Medical pharmacy (Clinical pharmacokinetics)

Research Keywords 【 Display / hide

  • Genetic variation・Epigeneitcs

Research Themes 【 Display / hide

  • Pharmacokinetics Pharmacodynamics/Drug interaction, Polymorphism/Epigenetics, 


     View Summary

    In order to optimize the medication based on the background of each patient, a variety of research for dosage adjustment using genetic information is in progress. However our understanding for individual variations of the efficacy and adverse reactions of medicines still remains to be further investigated. My research topics are the evaluation of the biological factors which affect the pharmacokinetics (and pharmacodynamics) and the extent of drug-drug interactions (DDI) as follows,
    (1) The effects of genetic and epigenetic factors on inter-individual differences of the protein expression and function of the metabolic enzyme and transporters
    The aim of this research topic is to evaluate the contribution of genetic and/or epigenetic factors such genetic polymorphism for cytochromeP450 enzyme and transporter and epigenetic regulation by microRNA etc on pharmacokinetic profiles certain drugs.


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

  • Evaluation of hepatic CYP3A enzyme activity using endogenous markers in lung cancer patients treated with cisplatin, dexamethasone, and aprepitant.

    Hibino H, Sakiyama N, Makino Y, Makihara-Ando R, Horinouti H, Fujiwara Y, Kanda S, Goto Y, Yoshida T, Okuma Y, Shinno Y, Murakami S, Shirasawa M, Watabe J, Jo H, Tamura N, Tanaka T, Arakawa S, Takamizawa S, Hashimoto H, Akiyoshi T, Imaoka A, Ohe Y, Yamaguchi M, Ohtani H.

    Eur J Clin Pharmacol. Accepted 2022.01

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0031-6970

  • Mechanistic bottom-up estimation of passive drug absorption from the gastrointestinal tract – Comparison among primary cultured human intestinal cells, Caco-2 cells, artificial membrane, and animal scale-up –

    Tsuchitani T, Akiyoshi T, Imaoka A, Ohtani H.

    Int J Clin Pharmacol Ther In press 2021.12

    Research paper (scientific journal), Joint Work, Accepted

  • Analysis of inhibition kinetics of three beverage ingredients, bergamottin, dihydroxybergamottin and resveratrol, on CYP2C9 activity.

    Akiyoshi T, Uchiyama M, Inada R, Imaoka A, Ohtani H.

    Drug metabolism and pharmacokinetics (Drug Metabolism and Pharmacokinetics)  In press   100429 2021.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1347-4367

     View Summary

    Some grapefruit juice (GFJ) ingredients and resveratrol, a fruit-derived phytoalexin, are known to inhibit cytochrome P450 (CYP) 2C9. However, their inhibition modes and detailed inhibition kinetics remain undetermined. This study aimed to investigate the inhibitory effects of two GFJ ingredients, bergamottin (BG) and dihydroxybergamottin (DHB), and resveratrol on CYP2C9 activity in vitro. DHB inhibited CYP2C9 activity, as assessed by warfarin 7-hydroxylation, in a preincubation time-dependent manner (i.e., mechanism-based inhibition; MBI), in the same manner as CYP2C19 and CYP3A4. The maximal inactivation rate (kinact,max) was 0.0638 min−1 and 0.12- and 0.26-fold of that for CYP2C19 and CYP3A4, respectively. BG showed both MBI and time-independent competitive inhibition. Resveratrol showed non-competitive inhibition with an inhibition constant (Ki) of 3.64 μM. Unlike the inhibition of CYP2C19 and CYP3A4, resveratrol did not induce MBI. These findings are important for estimating the risk of drug interactions between CYP2C9 substrates and some beverages. (146 words)

  • Time-dependent inhibition of CYP3A4-mediated midazolam metabolism by macrolide antibiotics in CYP3A4 genetic variants: Comparison with testosterone metabolism.

    Akiyoshi T, Naitou R, Imaoka A, Miyazaki M, Guengerich FP, Nakamura K, Yamamoto K, Ohtani H

    International journal of clinical pharmacology and therapeutics (International journal of clinical pharmacology and therapeutics)  59 ( 12 ) 745 - 752 2021.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0946-1965

     View Summary

    OBJECTIVES: The present study aimed to evaluate the effects of CYP3A4 genetic variation on the kinetics of mechanism-based inhibition (MBI) of both inhibitors using midazolam as a substrate for comparison with our previous study, as midazolam and testosterone have different binding sites. BACKGROUND: The genetic variation of cytochrome P450 (CYP) 3A4 affects MBI, expressed as the maximum inactivation rate constant (kinact,max) and the inhibitor concentration required to achieve half-maximal inactivation (KI). We previously showed, using testosterone as a substrate, that the MBI kinetics of erythromycin and clarithromycin differ among CYP3A4 variants. MATERIALS AND METHODS: Midazolam 1'-hydroxylation inactivation profiles of erythromycin and clarithromycin were assessed using recombinant CYP3A4.1, .2, .7, .16, and .18 expressed in Escherichia coli. MBI parameters were calculated from changes in the inactivation rate constant (Δkobs) by the inhibitors. RESULTS: Both inhibitors increased Δkobs value in a concentration- and preincubation time-dependent manner, and MBI kinetics differed among variants. Trends of differences in MBI parameters among variants were similar to those assessed using testosterone as a substrate; KI decreased for CYP3A4.7, and kinact,max decreased for CYP3A4.2, .7, and .16. CONCLUSION: The genetic variation of recombinant CYP3A4 affects the MBI profile of CYP3A4 by erythromycin and clarithromycin, while the influence of genetic variation was similarly observed regardless of substrates. Our findings are of clinical relevance because the residual enzyme activity of CYP3A4 in the presence of inhibitor was estimated to vary among genetic variants.

  • Dual kinetics of OATP2B1: Inhibitory potency and pH-dependence of OATP2B1 inhibitors.

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

    Drug metabolism and pharmacokinetics (Drug Metabolism and Pharmacokinetics)  41   100416 2021.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1347-4367

     View Summary

    Organic anion transporting polypeptide (OATP) 2B1 is expressed in the intestine and liver, and OATP2B1-mediated transport of estrone 3-sulfate is pH-dependent and consists of: the high-affinity component (Hc) and low-affinity component (Lc). This study aimed to evaluate the influence of pH on the transport kinetics of each component, along with the inhibitory nature of ten OATP2B1 inhibitors. The Michaelis constants (Km) were 4-fold and 1.5-fold lower at pH 6.3 than at pH 7.4, for Hc and Lc respectively. The inhibitory potencies of diclofenac, indomethacin, and ibuprofen towards Hc were 1.5–4.3 fold lower at pH 6.3 than at pH 7.4. Contrastingly, inhibitory potencies towards Lc were 9.0–52 fold lower at pH 7.4. Similarly, the inhibitory effect of naproxen was stronger towards Hc at pH 6.3 and towards Lc at pH 7.4. On the other hand, celecoxib selectively inhibited Lc transport at pH 7.4. Rifampicin inhibited both components at pH 6.3 and 7.4 to a similar extent, while bromosulphophthalein, naringin, and gefitinib selectively inhibited Hc irrespective of pH. Fexofenadine inhibited neither component. In conclusion, the transport affinities of both Hc and Lc were enhanced under acidic conditions. The influence of pH on the inhibitory potency towards each component varied among the inhibitors.

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

Reviews, Commentaries, etc. 【 Display / hide

  • 代謝酵素の変異は薬物相互作用に個人差をもたらすか? in silicoでのアプローチ

    酒井 悠輔, 宮崎 乃絵, 秋好 健志, 今岡 鮎子, 大谷 壽一

    日本医薬品情報学会総会・学術大会講演要旨集 ((一社)日本医薬品情報学会)  23回   81 - 81 2021.06

  • 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

  • The quantitative targeted absolute proteomics analysis of OATP1A2/2B1 meditated transport

    片岡寛樹, 秋好健志, 森田時生, 矢島広大, 今岡鮎子, 片山和浩, 内田康雄, 寺崎哲也, 大谷壽一.

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム (沖縄) , 2021.07, Poster (general), 日本薬学会

  • The effect of pH condition on metabolic profiles of CYP2C19 variants

    池田理紗, 秋好健志, 関 博行, 今岡鮎子, 山崎浩史, 下地みゆき, 中村克徳, 大谷壽一.

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム (沖縄) , 2021.07, Poster (general), 日本薬学会

  • Time-dependent inhibition profiles of fruit-components on CYP2C19genetic variants mediated metabolism

    2) 関博行, 秋好健志, 下地みゆき, 今岡鮎子, 山崎浩史, 中村克徳, 大谷壽一.

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム. (沖縄) , 2021.07, Poster (general), 日本薬学会

  • The influence of *23 allele on the CYP2C19 metabolic kinetics.

    渡辺大智, 栗田祐作, 秋好健志, 関博行, 今岡鮎子, 村山典恵, 山崎浩史, 下地みゆき, 中村克徳, 大谷壽一.

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム (沖縄) , 2021.07, Poster (general), 日本薬学会

  • The evaluation of fexofenadine transport kinetics mediated by OATP1A2 genetic variants

    韓 弘燁, 森田時生, 秋好健志, 片岡寛樹, 今岡鮎子, 片山和浩, 大谷壽一.

    医療薬学フォーラム2021/第29回クリニカルファーマシーシンポジウム (沖縄) , 2021.07, Poster (general), 日本薬学会

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

  • In silico analysis of DDI risk on Rare and Low-frequency variants in human CYPs and OATPs


    Japan Research Foundation for Clinical Pharmacology , 2021 年度(第 46 回) 研究奨励金, Takeshi Akiyoshi, Hisakazu Ohtani, Research grant, Principal Investigator

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    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, Research grant, Principal Investigator

  • 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


    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, Research grant, 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~


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


    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

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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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