Ketoconazole-Induced Reduction in Serum 1,25-Dihydroxyvitamin D*

Abstract

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 inserum 1,25-dihydroxyvitamin D levels (r = − 0.64; P < 0.001). At the highest dose taken byeach 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) us. 39 ± 3 pg⁄ml; P < 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 disordersof calcium metabolism and in treatment of patients with hypercalcemic disorders or renal stone disease.