Effect of ketoconazole and miconazole on 25-hydroxyvitamin D3 metabolism by cultured chick kidney cells.
The antifungal imidazoles, ketoconazole and miconazole, were tested for effects on 25-hydroxyvitamin D3 metabolism in primary cultures of chick kidney cells. Both behave as competitive inhibitors of 1-hydroxylation of 25-OH-D3 with approximate Ki's of 0.8 and 5.0 microM for ketoconazole and miconazole, respectively. Ketoconazole was as effective when added at the same time as the substrate as when the cells were preincubated with the compound. Ketoconazole also inhibited the production of 24,25(OH)2D3 in cells in which this activity was induced by 1,24(OH)2D3. The data suggest that therapeutic doses of these antifungal imidazoles could affect vitamin D status and calcium metabolism.
D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D002117:Calcitriol / Q000096:biosynthesis; D002478:Cells, Cultured; D002645:Chickens; D007654:Ketoconazole / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008825:Miconazole / Q000494:pharmacology*
D008825:Miconazole; D002117:Calcitriol; D002112:Calcifediol; D007654:Ketoconazole