Chlorpromazine metabolism in extracts of liver and small intestine from guinea pig and from man
Hartmann, F.; Gruenke, L.D.; Craig, J.C.; Bissell, D.M.
Drug Metabolism and Disposition the Biological Fate of Chemicals 11(3): 244-248
1983
ISSN/ISBN: 0090-9556 PMID: 6135583 Document Number: 204949
The metabolism of chlorpromazine approach was utilized to measure primary metabolites generated by these extracts, including the S-oxide, N-oxide, 7-hydroxyl, desmethyl and didesmethyl species. In short-term incubations (< 30 min), the measured metabolites accounted for at least 90% of the substrate utilized. Chlorpromazine metabolism differed strikingly both between species and between hepatic and intestinal tissues of the same species. Guinea pig hepatic microsomes were the most active of the preparations studied, producing relatively large amounts of N-oxide. Human hepatic microsomes produced the 7-hydroxyl metabolite predominantly, with minimal formation of N-oxide. Extracts of guinea pig intestinal mucosa formed the desmethyl and S-oxide products; an extract of duodenal mucosa from a healthy accident victim exhibited minimal metabolism of chlorpromazine. The kinetics of metabolite formation and studies with inhibitors of cytochrome P-450 suggested the involvement of multiple microsomal enzymes in chlorpromazine metabolism.