Biol. Pharm. Bull. 29(9) 1983—1985 (2006)
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چکیده
racemate. S-Enantiomer of warfarin has 3 to 5 times higher anticoagulant activity than the R-enantiomer. Therefore, changes in the disposition of S-warfarin will affect more significantly to its anti-coagulation activity of warfarin than that of R-warfarin. S-Warfarin is mainly metabolized to 7-hydroxylated metabolite by cytochrome P450 2C9 (CYP2C9). More than 10 genotypes of CYP2C9 are demonstrated, and major genotypes of CYP2C9 are CYP2C9*1 and CYP2C9*3 in Asian people. Sulfonylurea anti-diabetic drugs such as glimepiride, glibenclamide, and tolbutamide were also metabolized by CYP2C9. Recently, it has been reported that persons having CYP2C9*3 genotypes show higher AUC and longer elimination half-life of both glimepiride and glibenclamide after oral administration of these drugs. Tolbutamide and glibenclamide inhibit the metabolism of warfarin to 7-hyroxy metabolite by human liver microsomes in a competitive manner. However, little information of the metabolic interaction between warfarin and glimepiride has been obtained. We have investigated the effect of glimepiride on metabolism of S-warfarin to 7-hydroxywarfarin using recombinant cytochrome P450 2C9 microsomes (CYP2C9.1 and CYP2C9.3) and human liver microsomes, and have compared with the results from the experiments using glibenclamide as an inhibitor of CYP2C9.
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Antiinflammatory Constituents of Teramnus labialis
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