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)

医学部 病院薬剤学教室 , 薬学部_臨床薬物動態学講座 (信濃町)

職名

専任講師

HP

総合紹介 【 表示 / 非表示

学位 【 表示 / 非表示

  • 博士(薬学), 福岡大学, 論文, 2008年03月

免許・資格 【 表示 / 非表示

  • 薬剤師, 2001年05月

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 医療薬学 (臨床薬物動態学)

研究キーワード 【 表示 / 非表示

  • 遺伝的変異・エピジェネティクス

研究テーマ 【 表示 / 非表示

  • Pharmacokinetics Pharmacodynamics/Drug interaction, Polymorphism/Epigenetics, 

    2008年
    -
    継続中

     研究概要を見る

    患者背景に基づいた薬物治療の個別化を目的に、薬物の体内動態や相互作用の程度を変動させ、個人差の要因となる様々な生化学的影響因子について以下の研究を展開しています。
    (1) 薬物代謝酵素やトランスポータの発現や機能に対する遺伝的影響因子と後天的制御因子に関する検討
    薬物の吸収や消失に寄与する様々な生体機能蛋白は当該遺伝子の多型など先天的制御によってその発現量や機能の変化が引き起こされます。一方で、それら生体機能蛋白は、様々な環境下(疾患や薬剤暴露など)において post transcriptionalな発現制御や、発現後の安定性の制御を受けています。これらの先天的または後天的制御因子が、薬物動態学的パラメータに与える影響について、遺伝子多型や、microRNA によるmRNA の分解や転写抑制などを中心に研究を進め、それらを介した体内動態変動について評価しています。

 

著書 【 表示 / 非表示

  • 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

論文 【 表示 / 非表示

  • Comparison of the transport kinetics of fexofenadine and its pH dependency among OATP1A2 genetic variants.

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

    Drug metabolism and pharmacokinetics (Drug Metabolism and Pharmacokinetics)  47   100470 2022年08月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  1347-4367

     概要を見る

    Little is known about the influence of non-synonymous genetic variations in the organic anion-transporting polypeptide (OATP) 1A2 on the transport kinetics of its substrate fexofenadine. Moreover, the pH-dependency of fexofenadine uptake also remains unclear. This study aimed to evaluate the effects of genetic variants (Ile13Thr, Asn128Tyr, Glu172Asp, Ala187Thr, and Thr668Ser) on the OATP1A2-mediated uptake of fexofenadine at pH 6.3 and 7.4 and compare the pH dependency of OATP1A2-mediated uptake of fexofenadine and estrone 3-sulfate. The uptake clearances of 0.3 μM and 300 μM fexofenadine were compared with those of 0.3 μM and 300 μM estrone 3-sulfate at pH 6.3 and 7.4. Among the six variants examined, the Thr668Ser variant showed the highest fexofenadine uptake clearance (Vmax/Km); i.e., 4.53- and 6.28-fold higher uptake clearance than the wild type at pH 6.3 and 7.4, respectively. All variants exhibited significantly higher fexofenadine uptake at pH 6.3 than at pH 7.4. Compared with estrone 3-sulfate uptake, the uptake of 0.3 μM fexofenadine was less sensitive to pH. Our findings suggest that genetic variations in OATP1A2 may lead to altered intestinal absorption of fexofenadine, such as increased absorption in subjects bearing the Thr668Ser variant, which showed higher uptake activity.

  • Comparison of the inhibitory properties of the fruit component naringenin and its glycosides against OATP1A2 genetic variants.

    Araki N, Morita T, Akiyoshi T, Kataoka H, Yajima K, Katayama K, Imaoka A, Ohtani H

    Drug metabolism and pharmacokinetics (Drug Metabolism and Pharmacokinetics)  46   100464 2022年05月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  1347-4367

     概要を見る

    Non-synonymous genetic variants of organic anion-transporting polypeptide (OATP) 1A2 with altered transport activity have been identified. Naringin and narirutin, which are found in grapefruit, and their aglycon naringenin inhibit OATP1A2. However, their inhibitory effects on OATP1A2 variants have not been investigated, nor has the influence of their molecular structure, such as the number of sugar moieties, on their inhibitory potency. This study aimed to investigate the inhibitory effects of naringenin, its monosaccharide glycoside prunin, and its disaccharide glycosides naringin and narirutin on fexofenadine (FEX) uptake by OATP1A2 variants (Ile13Thr, Asn128Tyr, Ala187Thr, and Thr668Ser). Naringin, narirutin, and prunin inhibited FEX (0.3 μM) uptake by all of the examined OATP1A2 variants in a concentration-dependent manner. Compared with those for the wild type, the inhibition constants (Ki) of naringin, narirutin, and prunin for the Ala187Thr variant were significantly increased by 3.36-fold, 7.55-fold, and 10.6-fold, respectively. Naringenin inhibited all of the OATP1A2 variants, except Ala187Thr, concentration-dependently. The order of inhibitory potency was as follows for all variants: aglycone > monosaccharide glycoside > disaccharide glycosides. These results suggest that the Ala187Thr variant is less vulnerable to inhibition by naringenin and its glycosides. Moreover, greater glycosylation of naringenin reduces its inhibitory potency against OATP1A2.

  • 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

    International journal of clinical pharmacology and therapeutics (International journal of clinical pharmacology and therapeutics)  60 ( 5 ) 217 - 224 2022年03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 fraction of drug absorbed (Fa) from the intestine is an important parameter to characterize the pharmacokinetics of a drug. We aimed to search for an experimental system that provides the best parameters for estimating the effective permeability (Peff) used for the bottom-up prediction of Fa. MATERIALS AND METHODS: The absorption kinetics of 12 passively absorbed drugs were simulated by a compartment absorption transit (CAT) model using absorption parameters from four different experimental systems: human intestinal epithelial cell (HIEC) monolayer, Caco-2 monolayer, parallel artificial membrane permeability assay (PAMPA), and in situ rat intestinal perfusion. All absorption parameters were obtained from the literature. The in vitro apparent permeability coefficient (Papp) and rat in situ Peff were converted to human Peff using a bottom-up approach for each region, based on the morphological features of the human intestine. The simulated Fa values were compared to the respective observed values. Furthermore, plasma concentration profiles of the drugs were simulated by convolution using the time-course of the absorption rate simulated using the Peff values calculated from the HIEC Papp. RESULTS: The Fa values were best predicted by using the Peff values calculated from HEIC, within a 1.3-fold range of observed Fa in 11 out of 12 drugs. The simulated Cmax values of pharmacokinetic simulation using HIEC Papp fell within a 1.5-fold range of observed values for all the drugs examined. CONCLUSION: The HIEC monolayer was identified as the most suitable permeation parameter for estimating Fa and Cmax using a morphological feature-based bottom-up approach.

  • Inhibitory effects of cranberry juice and its components on intestinal OATP1A2 and OATP2B1: Identification of avicularin as a novel inhibitor

    Morita T, Akiyoshi T, Tsuchitani T, Kataoka H, Araki N, Yajima K, Katayama K, Imaoka A, Ohtani H

    J Agric Food Chem (Journal of Agricultural and Food Chemistry)  In press ( 10 ) 3310 - 3320 2022年02月

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

     概要を見る

    Organic anion-transporting polypeptide (OATP) 1A2 and OATP2B1 mediate the intestinal absorption of drugs. This study aimed to identify fruit juices or fruit juice components that inhibit OATPs and assess the risk of associated food-drug interactions. Inhibitory potency was assessed by examining the uptake of [3H]estrone 3-sulfate and [3H]fexofenadine into HEK293 cells expressing OATP1A2 or OATP2B1. In vivo experiments were conducted using mice to evaluate the effects of cranberry juice on the pharmacokinetics of orally administered fexofenadine. Of eight examined fruit juices, cranberry juice inhibited the functions of both OATPs most potently. Avicularin, a component of cranberry juice, was identified as a novel OATP inhibitor. It exhibited IC50 values of 9.0 and 37 μM for the inhibition of estrone 3-sulfate uptake mediated by OATP1A2 and OATP2B1, respectively. A pharmacokinetic experiment revealed that fexofenadine exposure was significantly reduced (by 50%) by cranberry juice. Cranberry juice may cause drug interactions with OATP substrates.

  • 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, Horinouchi H, Fujiwara Y, Kanda S, Goto Y, Yoshida T, Okuma Y, Shinno Y, Murakami S, Hashimoto H, Akiyoshi T, Imaoka A, Ohe Y, Yamaguchi M, Ohtani H

    European journal of clinical pharmacology (European Journal of Clinical Pharmacology)  Accepted ( 4 ) 613 - 621 2022年01月

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

     概要を見る

    Purpose: Aprepitant is used with dexamethasone and 5-HT3 receptor antagonists as an antiemetic treatment for chemotherapy, including cisplatin. Aprepitant is a substrate of cytochrome P450 (CYP) 3A4 and is known to cause its inhibition and induction. In addition, dexamethasone is a CYP3A4 substrate that induces CYP3A4 and CYP3A5 expression. In this study, we aimed to quantitatively evaluate the profile of CYP3A activity using its endogenous markers in non-small cell lung cancer patients receiving a standard cisplatin regimen with antiemetics, including aprepitant. Methods: Urinary 11β-hydroxytestosterone (11β-OHT)/testosterone concentration ratio and plasma 4β-hydroxycholesterol (4β-OHC) concentrations were measured before and after cisplatin treatment (days 1, 4, and 8). CYP3A5 was genotyped, and plasma aprepitant concentrations were measured on day 4 to examine its influence on CYP3A endogenous markers. Results: The urinary 11β-OHT/testosterone concentration ratio in the 35 patients included in this study increased by 2.65-fold and 1.21-fold on days 4 and 8 compared with day 1, respectively. Their plasma 4β-OHC concentration increased by 1.46-fold and 1.66-fold, respectively. The mean plasma aprepitant concentration on day 4 was 1,451 ng/mL, which is far lower than its inhibitory constant. The allele frequencies of CYP3A5*1 and CYP3A5*3 were 0.229 and 0.771, respectively. In patients with the CYP3A5*1 allele, the plasma 4β-OHC concentration was significantly lower at baseline but more potently increased with chemotherapy. Conclusion: CYP3A activity was significantly induced from day 4 to day 8 in patients receiving cisplatin and three antiemetic drugs.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • 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

    記事・総説・解説・論説等(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

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

研究発表 【 表示 / 非表示

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競争的研究費の研究課題 【 表示 / 非表示

  • フェキソフェナジンと解熱鎮痛剤の相互作用のリスク評価と個人間変動解析

    2022年05月
    -
    2023年06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, 研究助成金, 補助金,  研究代表者

  • 低頻度バリアント保有者における薬物相互作用リスク の予測精度を改善するための in silico 研究

    2021年12月
    -
    2023年10月

    公益財団法人 臨床薬理研究振興財団, 2021 年度(第 46 回) 研究奨励金, 秋好健志、大谷壽一, 補助金,  研究代表者

  • 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,  研究代表者

  • 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
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    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,  研究代表者

  • 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,  研究代表者

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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

  • 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

  • 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

    2022年度

  • 課題研究(臨床薬物動態学)

    2022年度

  • 演習(臨床薬物動態学)

    2022年度

  • 卒業研究1(薬学科)

    2022年度

  • 実務実習事前学習2

    2022年度

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