The effect of chronic oral ketoconazole on in vivo drug metabolism in the rat.

To verify the potential in vivo effects of ketoconazole, an antifungal agent with a wide spectrum of activity, on liver function, caffeine and phenytoin were chosen as probes for hepatic oxidative drug metabolism. Chronic treatment with ketoconazole (80 mg/kg oral) in the rat did not affect both pharmacokinetic profile of probes and a few biochemical parameters related to liver functions. These results indicate that further specific hepatic drug-metabolizing monoxygenase activities responsible to ketoconazole are to be identified to explain ketoconazole-drug interactions reported in vivo.