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ID 57264
著者
Matsumoto, Jun Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID researchmap
Nakamura, Hiroyoshi Department of Pharmaceutical Sciences, International University of Health and Welfare
San, Su Nwe Graduate School of Pharmaceutical Sciences, International University of Health and Welfare
Sato, Hikari Department of Pharmaceutical Sciences, International University of Health and Welfare
Takezawa, Manami Department of Pharmaceutical Sciences, International University of Health and Welfare
Kishi, Ryuto Department of Pharmaceutical Sciences, International University of Health and Welfare
Kito, Yutaro Department of Pharmaceutical Sciences, International University of Health and Welfare
Sugano, Junko Department of Pharmaceutical Sciences, International University of Health and Welfare
Izuki, Mai Department of Pharmaceutical Sciences, International University of Health and Welfare
Yanagisawa, Nao Department of Pharmaceutical Sciences, International University of Health and Welfare
Ikeda, Naoki Department of Pharmaceutical Sciences, International University of Health and Welfare
Saito, Yusuke Department of Pharmaceutical Sciences, International University of Health and Welfare
Kato, Yoshinori Department of Pharmaceutical Sciences, International University of Health and Welfare
Yamada, Harumi Department of Pharmaceutical Sciences, International University of Health and Welfare
Fujiyoshi, Masachika Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ariyoshi, Noritaka Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
抄録
Purpose
The cytochrome P450 (CYP) 3A family of enzymes metabolize the majority of clinically used drugs. CYP3A4 and CYP3A5 are the two major CYP3A isoforms, but exhinbit different substrate specificity. The aim of this study was to establish a simple screening method to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.
Methods
A screening method was developed based on competitive inhibition using luciferin-PPXE (L-PPXE), a luminogenic CYP3A substrate. CYP3cide, tacrolimus, and midazolam were selected as standard compounds metabolized by CYP3A4 or CYP3A5. Nine clinically-used drugs were evaluated for their abilities to inhibit luminescence resulting from L-PPXE metabolism. Appropriate reaction conditions for the screening method were determined using recombinant CYP3A4 and CYP3A5.
Results
A significant decrease in luminescence resulting from L-PPXE metabolism by CYP3A4 and CYP3A5 was observed only for drugs reported to be metabolized by CYP3As. The substrate specificities of CYP3A4 or CYP3A5 for the proposed CYP3A substrates using our screening method were consistent with those of previous reports or available drug information from pharmaceutical companies. The reaction volume for this method was 50 μL, and the time required for the entire procedure was 70 min. Furthermore, this screening can be performed using a single tube with minimal training.
Conclusions
Through the establishment of our screening method in the present study, we are sure it is useful to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.
キーワード
CYP3A
CYP3A5*3 allele
P450 Glo Assay system
Pharmacokinetics
Pharmacogenetics
備考
This fulltext will be available in Sep 2020
発行日
2019-07-31
出版物タイトル
Personalized Medicine Universe
8巻
出版者
Elsevier B.V.
開始ページ
41
終了ページ
44
ISSN
21867070
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
DOI
関連URL
isVersionOf https://doi.org/10.1016/j.pmu.2019.04.001
ライセンス
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
Citation
Jun Matsumoto, Hiroyoshi Nakamura, Su Nwe San, Hikari Sato, Manami Takezawa, Ryuto Kishi, Yutaro Kito, Junko Sugano, Mai Izuki, Nao Yanagisawa, Naoki Ikeda, Yusuke Saito, Yoshinori Kato, Harumi Yamada, Masachika Fujiyoshi, Noritaka Ariyoshi, A proposed simple screening method to determine relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro, Personalized Medicine Universe, Volume 8, 2019, Pages 41-44, ISSN 2186-4950, https://doi.org/10.1016/j.pmu.2019.04.001.
オープンアクセス(出版社)
非OA
オープンアーカイブ(出版社)
非OpenArchive