IN-VITRO AND IN-VIVO OXIDATIVE BIOTRANSFORMATION IN THE WEST-AFRICAN DWARF GOAT (CAPRUS-HIRCUS-AEGAGRUS) - SUBSTRATE ACTIVITIES AND EFFECTSOF INDUCERS

1. Cytochrome P450 activities in vivo and in vitro and enzyme inductio n by phenobarbital, beta-naphthoflavone, isoniazid and triacetyloleand omycin were investigated in the female dwarf goat. In vivo kinetics of antipyrine, sulphadimidine and caffeine were studied separately and a s a combination ('cocktail'). After establishing a lack of interaction between these compounds the effects of the inducing agents were inves tigated. lit vitro, hepatic microsomal enzyme activities and apoprotei n levels were determined. 2. In the beta-naphthoflavone treated goat, the microsomal ethoxy-resorufin-O-deethylation rate was markedly incre ased. beta-naphthoflavone also induced caffeine plasma clearance but d id not affect microsomal caffeine 1- and 3-demethylation rates. After phenobarbital treatment, caffeine plasma clearance was also increased. In contrast with beta-naphthoflavone treatment, phenobarbital treatme nt resulted in an increase of microsomal caffeine 1- and 3-demethylati on rates. 3. Goat liver microsomes were able to hydroxylate tolbutamid e, predominantly a CYP2C9 activity in man, and debrisoquine, a CYP2D a ctivity in different species. These activities were not affected by ei ther beta-naphthoflavone or phenobarbital. Sulphaphenazole was found t o be a more potent inhibitor of tolbutamide hydroxylation than sulphad imethoxine. Quinine was a more potent inhibitor of debrisoquine hydrox ylation than was quinidine. 4. As expected, the microsomal aniline-4-h ydroxylation rate (CYP2E) was increased after isoniazid treatment. 5. The microsomal testosterone 6 beta-hydroxylation rate (CYP3A) was incr eased after phenobarbital and triacetyloleandomycin treatment. Antipyr ine plasma clearance was also increased after phenobarbital treatment. 6. As cytochrome P450 activities and inducibility in the dwarf goat s how many resemblances to those in man, they may be of value as a model for human biotransformation research.