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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 CYP2C9.3), 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/*1 or CYP2C9*1/*3. The apparent K(i) 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.

Effect of Glimepiride and Glibenclamide on S-Warfarin 7-Hydroxylation by Human Liver Microsomes, Recombinant Human CYP2C9.1 and CYP2C9.3