In-vivo effects of itraconazole on hepatic mixed-function oxidase.

The effects of itraconazole, a triazole antifungal agent, on cytochrome P450 were investigated by measuring the anti-convulsant activity of phenytoin in mice, and zoxazolamine paralysis time, tolbutamide clearance, and plasma dicoumarol concentrations after a single injection of dicoumarol, in rats. Itraconazole, given either as a single dose of 5 or 10 mg/kg, or daily at these levels for five days, had no significant effect on any of the measures. The drug therefore appears to be free of enzyme inhibiting or inducing activity, although an effect on other cytochrome P450 isozymes can not be discounted. Thus itraconazole may possibly show fewer clinically significant drug interactions at the level of hepatic mixed function oxidase than other azole antifungal agents.