Stereoselective Reductive Metabolism of Metyrapone and Inhibitory Activity of Metyrapone Metabolites, Metyrapol Enantiomers, on Steroid 11β-Hydroxylase in the Rat
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概要
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Pharmacokinetics of metyrapone and metyrapol enantiomers was studied in the rat to determine the stereoselective reductive metabolism of metyrapone. The HPLC method using a chiral column was developed for the stereoselective analysis of metyrapol enantiomers in rat plasma. The AUC ratio of (-)- and (+)-metyrapol appeared in rat plasma after i.v. administration of metyrapone was about 3 : 1. The interconversion of (-)- or (+)-metyrapol to its antipode was negligible, and the reverse reaction from metyrapol to metyrapone was insignificant. There were similar kinetic parameters of (-)-metyrapol to those of (+)-metyrapol after i.v. administration of racemic metyrapol. These results indicate metyrapone displays product-stereoselective reductive metabolism in the rat. The inhibition of steroid 11β-hydroxylase by metyrapone, racemic metyrapol, (-)-metyrapol or (+)-metyrapol was analyzed in rat adrenal homogenates. Metyrapol was equally as potent as metyrapone in the inhibition of steroid 11β-hydroxylase and each enantiomer of metyrapol showed similar inhibitory activity on the rat adrenal steroid 11β-hydroxylase. These results indicate there is an insignificant difference in the inhibitory effects on steroid 11β-hydroxylase of metyrapol enantiomers, and that the inhibitory effects of metyrapol may be involved in the pharmacological activity of metyrapone in vivo.
- 公益社団法人日本薬学会の論文
- 1997-02-15
著者
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IWAKAWA Seigo
Department of Pharmaceutics, Kobe Pharmaceutical University
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Iwakawa Seigo
Department Of Hospital Pharmacy School Of Medicine Kobe University : Department Of Pharmacy Kyoto Un
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Iwakawa Seigo
Department Of Pharmaceutics Kobe Pharmaceutical University
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Asada S
Department Of Pharmaceutics Kobe Pharmaceutical University
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NAGAMINE Sachiko
Department of Pharmaceutics, Kobe Pharmaceutical University
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HORISAKA Eri
Department of Pharmaceutics, Kobe Pharmaceutical University
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FUKUYAMA Yukari
Department of Pharmaceutics, Kobe Pharmaceutical University
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MAETANI Kiyomi
Department of Pharmaceutics, Kobe Pharmaceutical University
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MATSUZAWA Ryo
Department of Pharmaceutics, Kobe Pharmaceutical University
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ASADA Shozo
Department of Pharmaceutics, Kobe Pharmaceutical University
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Matsuzawa Ryo
Department Of Pharmaceutics Kobe Pharmaceutical University
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Maetani Kiyomi
Department Of Pharmaceutics Kobe Pharmaceutical University
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Horisaka E
Department Of Pharmaceutics Kobe Pharmaceutical University
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Nagamine S
Department Of Pharmaceutics Kobe Pharmaceutical University
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Fukuyama Yukari
Department Of Pharmaceutics Kobe Pharmaceutical University
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Iwakawa Seigo
Department of Cardiology, Miki
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