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Effect of glimepiride and glibenclamide on S-warfarin 7-hydroxylation by human liver microsomes, recombinant human CYP2C9.1 and CYP2C9.3

被引：17
作者：
Iwakawa, Seigo
Miyashita, Kenji
Hashimoto, Yasuaki
Kuroda, Tsutomu
机构：
[1] Kobe Pharmaceut Univ, Dept Pharmaceut, Higashinada Ku, Kobe, Hyogo 6588558, Japan
[2] Miki City Hosp, Dept Pharm, Miki, Kagawa 6730402, Japan
来源：
BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2006年 / 29卷 / 09期
关键词：
warfarin; glimepiride; liver microsome; CYP2C9; drug interaction; drug metabolism; ALLELIC VARIANT; IDENTIFICATION; (S)-WARFARIN; METABOLISM; HYDROXYLATION; POLYMORPHISM; GLYBURIDE; GENOTYPES;
D O I：
10.1248/bpb.29.1983
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The effect of glimepiride on metabolism of S-warfarin to 7-hydroxywarfarin was studied using human liver microsomes and recombinant cytochrome P450 2C9 microsomes (CYP2C9.1 and CYPX9.3), and was compared with the results from the experiments using glibenclamide as an inhibitor. S-Warfarin 7-hydroxylation by recombinant CYP2C9.1 and CYP2C9.3 was inhibited by glimepiride competitively. The apparent K-i value of glimepiride was lower at CYP2C9.3 than at CYP2C9.1. Glimepiride also inhibited 7-hydroxylation of S-warfarin in a competitive manner by microsomes from human liver which showed the genotypes of CYP2C9, as CYP2C9*1/*l or CYP2C9*1/*3. The apparent K, value of glimepiride was lower than that of glibenclamide. These results may provide valuable information for optimizing the anticoagulant activity of warfarin when glimepiride is co-administered to patients.
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收藏
页码：1983 / 1985
页数：3
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