Sex-dependent pharmacokinetics of S(-)-hydroxyhexamide, a pharmacologically active metabolite of acetohexamide, in rats. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. [Comp Biochem Physiol C Toxicol Pharmacol] Journal article

Title	Sex-dependent pharmacokinetics of S(-)-hydroxyhexamide, a pharmacologically active metabolite of acetohexamide, in rats.
Author(s)	Imamura Y, Kaneko M, Takada H, Otagiri M, Shimada H, Akita H
Institution	Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Kumamoto 862-0973, Japan. yorishig@gpo.kumamoto-u.ac.jp
Source	Comp Biochem Physiol C Toxicol Pharmacol 2002 Dec; 133(4):587-92.
MeSH	Acetohexamide Animals Female Male Rats Rats, Wistar Sex Characteristics
Abstract	The pharmacokinetic profile of S(-)-hydroxyhexamide (S-HH), a pharmacologically active metabolite of acetohexamide, was examined in male and female rats. S-HH was eliminated more rapidly from plasma in the males than in the females. A significant sex difference was observed in the pharmacokinetic parameters of S-HH in rats. Testectomy caused significant alteration in these parameters of S-HH in male rats, whereas ovariectomy did not in the females. The co-administration of sulfamethazine significantly decreased the plasma clearance (CL(p)) of S-HH in male rats, but had no effect in the females. The plasma concentrations of acetohexamide generated from S-HH showed no sex-related difference. Furthermore, there was no difference in the accumulation of S-HH by renal cortical slices from male and female rats. We propose the possibility that the sex-dependent pharmacokinetics of S-HH in rats is mediated through the male-specific hydroxylation of the cyclohexyl ring catalyzed by a major cytochrome p450 (CYP) isoform (CYP2C11), although the detailed mechanism remains to be elucidated.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	12458186

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