Sex-dependent pharmacokinetics and in vitro reductive metabolism of acetohexamide in Wistar-Imamichi rats

被引：0

作者：

Imamura, Y ^{[1
]}

Kaneko, M ^{[1
]}

Mori, Y ^{[1
]}

Otagiri, M ^{[1
]}

机构：

[1] Kumamoto Univ, Fac Pharmaceut Sci, Kumamoto 8620973, Japan

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 1999年 / 22卷 / 04期

关键词：

acetohexamide; sex-dependent pharmacokinetics; in vitro reductive metabolism; male-specific cytochrome P450; Wistar-Imamichi rat;

D O I：

暂无

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A significant sex-related difference was observed for the pharmacokinetics of acetohexamide in Wistar-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 decreased the CLp of acetohexamide in male Wistar-IM rats. Based on these results, it is reasonable to assume that the sex-dependent pharmacokinetics of acetohexamide observed in Wistar-IM rats is associated with the male-specific hydroxylation catalyzed by CYP2C11.

引用

页码：435 / 438

页数：4

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