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标题：Sex-Dependent Pharmacokinetics and in Vitro Reductive Metabolism of Acetohexamide in Wistar-Imamichi Rats
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作者：Yorishige IMAMURA ; Miho KANEKO ; Yukiko MORI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1999
卷号：22
期号：4
页码：435-438
DOI：10.1248/bpb.22.435
出版社：The Pharmaceutical Society of Japan
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 (CL_p) of acetohexamide in male rats, whereas ovariectomy had no effect on the CL_p 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 CL_p 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