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酮康唑：大鼠肝脏中细胞色素P - 450依赖性药物代谢的强效抑制剂。

Ketoconazole: a potent inhibitor of cytochrome P-450-dependent drug metabolism in rat liver.

作者信息

Sheets J J, Mason J I

出版信息

Drug Metab Dispos. 1984 Sep-Oct;12(5):603-6.

PMID:6149911
Abstract

Ketoconazole, an orally active imidazole antimycotic agent, is shown to be a potent inhibitor of drug N-demethylase activities of liver microsomes from rats pretreated with phenobarbital or pregnenolone-16 alpha-carbonitrile, and an inhibitor of 7-ethoxyresorufin O-deethylase activity of liver microsomes from rats pretreated with 5,6-benzoflavone. Spectrophotometric studies reveal that the imidazole compound binds to the cytochrome P-450 component of the monooxygenase complex, and has little effect on NADPH-cytochrome c (P-450) reductase activity. These results are strongly suggestive that cytochrome P-450 is the site of action of this potent inhibitor of drug metabolism in liver microsomes.

摘要

酮康唑是一种口服活性咪唑类抗真菌剂，它被证明是苯巴比妥或孕烯醇酮 - 16α - 腈预处理大鼠肝脏微粒体药物N - 脱甲基酶活性的强效抑制剂，也是5,6 - 苯并黄酮预处理大鼠肝脏微粒体7 - 乙氧基异吩恶唑酮O - 脱乙基酶活性的抑制剂。分光光度研究表明，该咪唑化合物与单加氧酶复合物的细胞色素P - 450成分结合，对NADPH - 细胞色素c（P - 450）还原酶活性影响很小。这些结果有力地表明细胞色素P - 450是这种肝脏微粒体中药物代谢强效抑制剂的作用位点。

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