EFFECT OF ARTANE ON THE RATE OF CHLORPROMAZINE METABOLISM IN MOUSE LIVER MICROSOMAL SYSTEM

In clinical treatment of psychosis artane is usually administered in combination with chlorpromazine(CPZ) to relieve the extrapyramidal side effects caused by CPZ. Several authors have reported that CPZ plasma level was lowered by artane because it inhibited the absorption of CPZ from the gastrointestinal tract.In the present investigation, the effect of artane on the rate of CPZ metabolism in mouse liver microsomal system was examined. It was found that after administration of artane in the dose range from 25 mg/kg to 87.5 mg/kg(i p daily) to mice for three days, the rate of CPZ metabolism by mouse liver microsomes in vitro was markedly increased, and the hepatic cytochrome P-450 concentration of mice was also increased significantly. The results indicate that artane possesses inducing effect on mouse liver drug metabolism enzymes. This may be the main cause of the increased rate of CPZ metabolism in liver microsomal system by artane.