摘要：A significant sex-related difference was observed for the pharmacokinetics of acetohexamide in Wister-Imamichi (Wistar-IM) rats. However, there was no sex difference of the in vitro reductive metabolism of acetohexamide in the liver or kidney of these rats. Testectomy was found to decrease the plasma clearance (CLp) of acetohexamide in male rats, whereas ovariectomy had no effect on the CLp of acetohexamide in female animals, suggesting that androgens regulate the pharmacokinetics of acetohexamide. The co-administration of sulfamethazine, which is known to be metabolized by a male-specific cytochrome P450 (CYP) isoform (CYP2C11), significantly decresed the CLp of acetohexamide in male Wister-IM rats. Based on these results, it is reasonable to assume that the sex-dependent pharmacokinetics of acetohexamide observed in Wister-IM rats is associated with the male-specific hydroxylation catalyzed by CYP2C11.
关键词：acetohexamide;sex-dependent pharmacokinetics;in vitro reductive metabolism;male-specific cytochrome P450;Wistar-Imamichi rat
