Inhibitory effects of sesamin on CYP2C9-dependent 7-hydroxylation of S-warfarin

被引：3

作者：

Fujii, Miharu ^{[1
]}

Yasuda, Kaori ^{[1
]}

Sakaki, Toshiyuki ^{[1
]}

机构：

[1] Toyama Prefectural Univ, Fac Engn, Dept Pharmaceut Engn, 5180 Kurokawa, Imizu, Toyama 9390398, Japan

来源：

DRUG METABOLISM AND PHARMACOKINETICS | 2020年 / 35卷 / 04期

关键词：

Sesamin; Warfarin; CYP2C9; Human liver microsomes; Competitive inhibition; ANTIOXIDATIVE METABOLITES; EPISESAMIN; LIVER; CYTOCHROME-P450; LIGNAN;

D O I：

10.1016/j.dmpk.2020.05.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A recent report demonstrated that sesamin strongly and non-competitively inhibits S-warfarin 7-hydroxylation activity in human liver microsomes with a K-i value of 0.2 mu M. This finding suggests that sesamin predominantly binds to CYP2C9 at another site for which it has a higher affinity than its affinity for the active site, thereby inhibiting the activity of CYP2C9 non-competitively. In this study, we found that sesamin competitively inhibited the 7-hydroxylation activity of S-warfarin in human liver microsomes with a K-i value of 15.7 mu M. In addition, the recombinant CYP2C9-dependent 7-hydroxylation activity of S-warfarin was competitively inhibited by sesamin with a Ki value of 13.1 mu M. These results are consistent with the fact that sesamin is a good substrate of CYP2C9, and its activity follows Michaelis-Menten kinetics. As the plasma concentration of sesamin after its administration is usually lower than 0.01 mu M, the inhibition of S-warfarin metabolism by sesamin does not appear to be severe. (C) 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

引用

页码：368 / 373

页数：6

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