文章基本信息

标题：Inhibition of Testosterone Biosynthesis in Testicular Microsomes by Various Imidazole Drugs. Comparative Study with Ketoconazole
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作者：Kunihiko MORITA ; Takeshi ONO ; Harumi SHIMAKAWA 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：1990
卷号：13
期号：6
页码：336-343
DOI：10.1248/bpb1978.13.336
出版社：The Pharmaceutical Society of Japan
摘要：Ketoconazole (KCZ), an imidazole-containing antimycotic, has been demonstrated to inhibit testosterone biosynthesis in man. In this study, the inhibitory activities of various imidazole drugs such as miconazole (MCZ), cimetidine (CIM), ozagrel (OZA) and its metabolites (M-1 and M-2) on the pathway of testosterone biosynthesis in testicular microsomes were compared with that of KCZ in vitro. Additionally, the changes in serum testosterone level in the patients by the treatments with MCZ were followed. KCZ inhibited 17α-hydroxylase and C^{17, 20}-lyase activities in a dose-depentent manner, while it did not affect 17β-hydroxysteroid dehydrogenase activity. Although the patterns of the inhibitory actions and the interaction of either imidazole drugs with cytochrome P-450 as 17α-hydroxylase and C_{17, 20}-lyase were similar to those of KCZ, the inhibitory potencies and affinities for the cytochrome P-450 system decreased in the order of KCZ>MCZ>OZA>M-2>M-1>CIM. At the end of the intravenous injection of 200 mg MCZ to the patients, the serum testosterone levels decreased by about 16% of the original level and then returned to the original level 5h after the end of injection. These results indicate that either imidazole drugs tested colud inhibit a cuytochrome P-450 enzyme C_{17, 20}-lyase mainly in testicular microsomes, and suggest that MCZ, a potent inhibitor subsequent to KCZ, induces a slight alteration in the testosterone biosynthesis in its clinical use.
关键词：C17, 20-lyase