Sex Difference in the Metabolism of Pirmenol in Rats

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概要

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• 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.

• 1997-12-15

著者

• Matsuki Yasuhiko

  Laboratory Of Analytical Chemistry Hatano Research Institute Food And Drug Safety Center

• Suzuki E

  Hoechst Marion Roussel Ltd. Kawagoe Jpn

• Suzuki Ei-ichiro

  Institute Of Life Sciences Ajinomoto Co Inc

• Kaneko K

  Department Of Pharmacology Showa Pharmaceutical University

• 鈴木 恵理香

  Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University

• NAKAGOMI Madoka

  Laboratory of Analytical Chemistry, Hatano Research Institute, Food and Drug Safety Center

• SUZUKI Emako

  Laboratory of Analytical Chemistry, Hatano Research Institute, Food and Drug Safety Center

• KITASHIMA Miiko

  Laboratory of Analytical Chemistry, Hatano Research Institute, Food and Drug Safety Center

• IIDA Sayaka

  Laboratory of Analytical Chemistry, Hatano Research Institute, Food and Drug Safety Center

• ABE Masahiro

  Laboratory of Analytical Chemistry, Hatano Research Institute, Food and Drug Safety Center

• KANEKO Kiyohisa

  Warner-Lambert K.K.,

• Kitashima Miiko

  Laboratory Of Analytical Chemistry Hatano Research Institute Food And Drug Safety Center

• Iida S

  Laboratory Of Analytical Chemistry Hatano Research Institute Food And Drug Safety Center

• Abe Masahiro

  Laboratory Of Analytical Chemistry Hatano Research Institute Food And Drug Safety Center

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