Inhibition of cytochrome P450 enzymes in the Australian brushtail possum, Trichosurus vulpecula: comparison with that of the rat, rabbit, sheep and chicken.

A comparative study was conducted of the inhibition of liver microsomal cytochrome P450 phase I biotransformation enzyme activity of the Australian brushtail possum, rat, rabbit, sheep and chicken. The possum has caused considerable agricultural and ecological problems since its introduction to New Zealand. This work investigated species differences in cytochrome P450 inhibition by selected imidazole derivatives that may be exploited for designing a more species-specific method of toxicological control of the New Zealand possum population. The imidazole derivatives used were ketoconazole, clotrimazole, miconazole and cimetidine. The potency of these inhibitors varied, with clotrimazole and miconazole being most potent, followed by ketoconazole. Cimetidine was the least effective inhibitor. The inhibitory effect of imidazole derivatives on cytochrome p450 phase I biotransformation enzymes appeared more effective in the possum than in other species. All inhibitors used produced type II spectra upon interaction with cytochrome P450 preparations. Possum and chicken microsomal preparations showed absorbancy maxima at 428 nm, rabbit and rat and 429 nm, and sheep at 431 nm.