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Journal of Clinical Endocrinology & Metabolism, Vol 63, 766-769, Copyright © 1986 by Endocrine Society

ARTICLES

Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D

AR Glass and C Eil

The antimycotic agent ketoconazole is known to inhibit several cytochrome P450-dependent enzymes involved in the biosynthesis of steroid hormones from cholesterol. Since 1,25-dihydroxyvitamin D is also a sterol synthesized by cytochrome P450-dependent enzymes, we assessed whether ketoconazole would lower serum 1,25-dihydroxyvitamin D levels. In nine normal men, administration of ketoconazole for 1 week in doses of 300-1200 mg/day led to a dose-dependent reduction in serum 1,25-dihydroxyvitamin D levels (r = -0.64; P less than 0.001). At the highest dose taken by each man (1200 mg/day in six, 900 mg/day in one, and 600 mg/day in two), serum levels of 1,25-dihydroxyvitamin D fell significantly compared to baseline [14 +/- 1 (+/- SEM) vs. 39 +/- 3 pg/ml; P less than 0.001), but there was no change in serum levels of 25-hydroxyvitamin D, PTH, calcium, phosphate, or alkaline phosphatase. Ketoconazole may be potentially useful in exploring the pathogenetic role of 1,25-dihydroxyvitamin D in disorders of calcium metabolism and in treatment of patients with hypercalcemic disorders or renal stone disease.


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