Effect of drug pretreatment on the metabolic oxidation of chlorpromazine in rat.
The metabolic oxidation of chlorpromazine (CPZ) was investigated after pretreatment of rats with some drugs and chemicals for 6 days. Pentobarbitone, gamma-collidine, ethanol, and anthracene induced a significant increase in both S-oxidation and 7-hydroxylation, whereas CPZ pretreatment increased mainly 7-hydroxylation. Metyrapone and safrole preferentially inhibited 7-hydroxylation. Chloroquine and quinine pretreatment increased urinary excretion of CPZ and its metabolites, probably due to occupation of CPZ-binding sites rather than as a result of enzyme induction.
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002746:Chlorpromazine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011292:Premedication; D011725:Pyridines / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000494:pharmacology
D000873:Anthracenes; D011725:Pyridines; D000431:Ethanol; C007106:gamma-collidine; D002738:Chloroquine; D011803:Quinine; C034020:anthracene; D010424:Pentobarbital; D012451:Safrole; D002746:Chlorpromazine; D008797:Metyrapone