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Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D
Ketoconazole, an antifungal drug, significantly lowers serum 1,25-dihydroxyvitamin D levels in a dose-dependent manner. This finding suggests potential therapeutic applications for hypercalcemic disorders.
Area of Science:
- Endocrinology
- Pharmacology
- Biochemistry
Background:
- Ketoconazole is known to inhibit cytochrome P450 enzymes.
- These enzymes are crucial for steroid hormone biosynthesis from cholesterol.
- 1,25-dihydroxyvitamin D is a sterol synthesized via cytochrome P450 pathways.
Purpose of the Study:
- To investigate the effect of ketoconazole on serum 1,25-dihydroxyvitamin D levels.
- To assess the potential role of ketoconazole in modulating vitamin D metabolism.
Main Methods:
- Nine healthy men received ketoconazole for one week.
- Doses ranged from 300-1200 mg/day.
- Serum levels of 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, calcium, phosphate, and alkaline phosphatase were measured.
Main Results:
- Ketoconazole administration resulted in a significant, dose-dependent reduction in serum 1,25-dihydroxyvitamin D.
- The highest doses (600-1200 mg/day) led to a substantial decrease in 1,25-dihydroxyvitamin D levels compared to baseline.
- No significant changes were observed in serum 25-hydroxyvitamin D, PTH, calcium, phosphate, or alkaline phosphatase.
Conclusions:
- Ketoconazole effectively lowers serum 1,25-dihydroxyvitamin D levels.
- This suggests ketoconazole's potential utility in studying the role of 1,25-dihydroxyvitamin D in calcium metabolism disorders.
- It may also be beneficial in treating hypercalcemic disorders and renal stone disease.
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