Engelhardt D, Weber M M, Miksch T, Abedinpour F, Jaspers C
Medical Department II, Klinikum Grosshadern, University of Munich, FR Germany.
Clin Endocrinol (Oxf). 1991 Aug;35(2):163-8. doi: 10.1111/j.1365-2265.1991.tb03516.x.
The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro.
After incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0-2000 microM), radioactive metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium-labelled precursors to products.
In vitro, ketoconazole showed a significant inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20-desmolase (IC50 2 microM), 16 alpha-hydroxylase (IC50 9 microM), 17 alpha-hydroxylase (IC50 18 microM), 18-hydroxylase (IC50 28 microM), and 11 beta-hydroxylase (IC50 35 microM). In the tested concentrations ketoconazole had no inhibitory effect on the 21-hydroxylase, the 3 beta-hydroxysteroid dehydrogenase and the 20-hydroxysteroid dehydrogenase component of the C17,20-desmolase enzyme system.
The data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17, 20-desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states.
