Couch R M, Muller J, Perry Y S, Winter J S
J Clin Endocrinol Metab. 1987 Sep;65(3):551-4. doi: 10.1210/jcem-65-3-551.
The kinetics of the inhibitory effects of the imidazole antimicrobial ketoconazole on the activities of the steroidogenic enzymes distal to cholesterol side-chain cleavage were studied in human adrenal microsomal and mitochondrial suspensions. Although ketoconazole was a competitive inhibitor of all five enzyme reactions, the effects on 17-hydroxylase, 17,20-desmolase, and 11-hydroxylase activities (Ki = 10(-8) M) were considerably greater than those on 21-hydroxylase and 3 beta-hydroxysteroid dehydrogenase/isomerase activities (Ki = 10(-4) M). These findings explain the clinical endocrine effects of ketoconazole in the usual therapeutic doses, which include inhibition of cortisol and androgen secretion, compensatory ACTH-mediated secretion of 17-desoxysteroids such as progesterone and aldosterone, and suppression of PRA.
在人肾上腺微粒体和线粒体悬浮液中研究了咪唑类抗真菌药酮康唑对胆固醇侧链裂解远端的甾体生成酶活性的抑制作用动力学。尽管酮康唑是所有五种酶反应的竞争性抑制剂，但对17-羟化酶、17,20-裂解酶和11-羟化酶活性（Ki = 10(-8) M）的影响远大于对21-羟化酶和3β-羟类固醇脱氢酶/异构酶活性（Ki = 10(-4) M）的影响。这些发现解释了酮康唑在常用治疗剂量下的临床内分泌效应，包括抑制皮质醇和雄激素分泌、促肾上腺皮质激素介导的17-脱氧类固醇如孕酮和醛固酮的代偿性分泌以及抑制肾素活性。
