In vitro effects of an imidazole antifungal,prochloraz, on spectral and catalytic properties of microsomal cytochromes P-450

1. The imidazole antifungal agent, prochloraz, elicited type II spectral interactions with microsomal cytochromes P-450 from rats pretreated with phenobarbital (PB), 3-methyl-cholanthrene (MC) and dexamethasone (DEX).

2. Prochloraz interacts strongly with type I binding sites of both PB-and DEX-induced cytochromes P-450 and to a lesser extent with cytochromes P-450 from MC-induced rats.

3. The antifungal derivative was a more potent inhibitor of the troleandomycin-nitrosoalkyl-cytochrome P-450 complex formation in DEX-induced microsomes than of the isosafrole-carbene-cytochrome P-450 complex formation in MC-pretreated rats.

4. Prochloraz is a strong inhibitor of the cytochrome P-450-dependent mixed-function oxidases in rat liver microsomal preparations.