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.
Rodrigues
A D
AD
Department of Biochemistry, University of Surrey, Guildford, U.K.
Waddell
P R
PR
Ioannides
C
C
D000818:Animals; D003022:Clotrimazole / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D006899:Mixed Function Oxygenases; D003022:Clotrimazole