Effect of ketoconazole on metabolism and binding of 1,25-dihydroxyvitamin D-3 by intact rat osteogenic sarcoma cells.

The antifungal imidazole, ketoconazole, was tested for effects on 1,25-dihydroxyvitamin D-3 (1,25-(OH)2D3) metabolism and binding in intact osteoblast-like osteogenic sarcoma cells (UMR-106). Ketoconazole inhibited the C-24 oxidation of 1,25-(OH)2D3 in a dose-dependent manner. Furthermore, inhibition of 1,25-(OH)2D3 metabolism by ketoconazole resulted, after a lag time of 2 h, in a sharp increase of receptor-bound 1,25-(OH)2D3. The data suggest that the self-induced 1,25-(OH)2D3 metabolism may play an important role in controlling the intracellular levels of and, consequently, receptor occupancy by the active form of vitamin D. Furthermore the results are compatible with the existence of a homologous up-regulation of the 1,25-(OH)2D3-receptor.