Miossec P, Archambeaud-Mouveroux F, Teissier M P
Service d'Endocrinologie-Diabétologie-Nutrition, Hôpital Jean Verdier, Bondy.
Ann Endocrinol (Paris). 1997;58(6):494-502.
Ketoconazole, a broad-spectrum imidazole antimycotic agent, interferes with cytochrome P-450 enzyme systems in several organs (testis, ovary, adrenal gland, kidney, liver). It inhibits cholesterol synthesis by a dose-dependent transient braking of the 14 alpha-demethylase. Steroidogenesis is inhibited by its action on the C17-20 lyase, the cholesterol side-chain cleavage enzyme and the 17 alpha-hydroxylase. In gonads it inhibits aromatase and adrenocortical steroid biosynthesis is also inhibited at the 11 beta-hydroxylation and 18-hydroxylation steps. Its antiandrogenic effect may be useful in the management of metastatic prostate carcinoma and in testotoxicosis, its usefulness in the treatment of hirsutism is more questionable. Its anticortisolic effect may be useful in most Cushing's syndromes, where drug control of hypercortisolism is suitable for patients undergoing surgery, as well as those in whom more definitive treatment is delayed. Its usefulness as inhibitor of vitamin D or mineralocorticoids requires further investigation.
酮康唑是一种广谱咪唑类抗真菌药，可干扰多个器官（睾丸、卵巢、肾上腺、肾脏、肝脏）中的细胞色素P-450酶系统。它通过剂量依赖性地短暂抑制14α-脱甲基酶来抑制胆固醇合成。其对C17-20裂解酶、胆固醇侧链裂解酶和17α-羟化酶的作用会抑制类固醇生成。在性腺中，它抑制芳香化酶，肾上腺皮质类固醇生物合成在11β-羟化和18-羟化步骤也受到抑制。其抗雄激素作用可能对转移性前列腺癌的治疗和睾丸中毒有用，但其在治疗多毛症方面的有效性更值得怀疑。其抗皮质醇作用可能对大多数库欣综合征有用，在这些综合征中，药物控制高皮质醇血症适用于接受手术的患者以及那些更明确治疗延迟的患者。其作为维生素D或盐皮质激素抑制剂的有效性需要进一步研究。
