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.