Inhibition of the rat hepatic mixed-function oxidases by in vivo administration of clotrimazole.

The ability of the 1-substituted imidazole antifungal agent clotrimazole to inhibit the rat hepatic microsomal mixed-function oxidases was investigated in rats pretreated with either phenobarbital or 3-methylcholanthrene. When administered to 3-methylcholanthrene-pretreated animals, clotrimazole inhibited the O-deethylations of ethoxyresorufin and ethoxycoumarin. An even more marked inhibition of the dealkylation of pentoxyresorufin and O-deethylation of ethoxycoumarin was observed in phenobarbital-pretreated rats. It is concluded that administration of clotrimazole to rats gives rise to a marked inhibition of the hepatic mixed-function oxidases, and especially of the cytochrome P450 II B family of haemoproteins.