Inhibition of steroidogenesis by ketoconazole - Therapeutic uses

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 C(17-20)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 metastic 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.