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标题：Sex Difference in the Metabolism of Pirmenol in Rats
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作者：Madoka NAKAGOMI ; Emako SUZUKI ; Miiko KITASHIMA 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：1997
卷号：20
期号：12
页码：1279-1284
DOI：10.1248/bpb.20.1279
出版社：The Pharmaceutical Society of Japan
摘要：The in vitro metabolism of pirmenol (cis-α-[3-(2, 6-dimethyl-1-piperidinyl)propyl]-α-phenyl-2-pyridinemethanol) and glucuronidation of its metabolites, a 4-hydroxylated derivative of pirmenol (M3) and 3-methylether of M3 (M5), were investigated using a hepatic 9000×g supernatant and microsomes, respectively, of female and male rats in order to elucidate the higher urinary excretion of M3G and M5G (glucuronides of M3 and M5, respectively) in females previously observed in in vivo metabolism. Pirmenol Δ^1' iminium ion (M2) and M3 were formed by the oxidation of pirmenol in both sexes; however, M2 was the main metabolite in males, while M2 and M3 were formed at nearly the same level in females. On glucuronidation of M3 and M5, the V_max values of both compounds were higher in female rats, consistent with the results in vivo. In addition, the sex difference in the urinary excretion ratio of M5G to M3G (1.1 in female, 2.5 in male) might reflect the lower availability of M3 for glucuronidation in male rats in vivo. The chromatographic separation of diastereomers of M5G was also described.
关键词：sex difference;glucuronidation;pirmenol;rat;in vitro metabolism