CLINICAL-SIGNIFICANCE OF INTERACTIONS WITH ANTIFUNGAL AGENTS

Antifungal drugs act by a variety of mechanisms. Agents such as substituent imidazoles and triazoles, which act by inhibiting the fungal cytochrome P-450-dependent enzyme lanosterol N-demethylase, have the potential to inhibit host cytochrome P-450-dependent drug metabolism. This is discussed with respect to ketoconazole, fluconazole and itraconazole. In contrast, allylamines, which have a different mode of action and a weaker ability to bind to cytochrome P-450, are not expected to inhibit clinical drug oxidation. Inducers of drug metabolism, especially rifampicin, phenobarbitone and phenytoin, may lower plasma (and tissue) concentrations of those antifungals metabolized by mixed function oxidases, with therapeutic consequences.