ALLAN PONT, M.D.; PAUL L. WILLIAMS, M.D.; DAVID S. LOOSE, Ph.D.; DAVID FELDMAN, M.D.; RICHARD E. REITZ, M.D.; CHARLOTTE BOCHRA; DAVID A. STEVENS, M.D.
Ketoconazole, a broad-spectrum, antifungal drug that is administered orally, has been shown to inhibit sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats. In healthy humans, the Cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose. The inhibition persisted for up to 8 hours and was absent by 16 hours. This finding indicated that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketoconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may prove useful as an agent to block steroid synthesis.
PONT A, WILLIAMS PL, LOOSE DS, FELDMAN D, REITZ RE, BOCHRA C, et al. Ketoconazole Blocks Adrenal Steroid Synthesis. Ann Intern Med. ;97:370–372. doi: 10.7326/0003-4819-97-3-370
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Published: Ann Intern Med. 1982;97(3):370-372.
Adrenal Disorders, Endocrine and Metabolism.
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