ID 57264
Author
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
Abstract
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.
Keywords
CYP3A
CYP3A5*3 allele
P450 Glo Assay system
Pharmacokinetics
Pharmacogenetics
Note
This fulltext will be available in Sep 2020
Published Date
2019-07-31
Publication Title
Personalized Medicine Universe
Volume
volume8
Publisher
Elsevier B.V.
Start Page
41
End Page
44
ISSN
21867070
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
File Version
author
DOI
Related Url
isVersionOf https://doi.org/10.1016/j.pmu.2019.04.001
License
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.
Open Access (Publisher)
non-OA
Open Archive (publisher)
Non-OpenArchive