安坦对氯丙嗪在肝微粒体中代谢速率的影响

本文以氯丙嗪为底物研究了安坦对小鼠肝微粒体药酶的诱导作用,发现当每日腹腔注射安坦25mg～87.5mg/kg时,连续三天,可使氯丙嗪在含有肝微粒体的体外反应系统中的代谢速率明显加快。安坦这种诱导作用的强度略高于苯巴比妥。小鼠用安坦后肝微粒体中细胞色素P-450含量显著提高,这可能是安坦能加速氯丙嗪体外代谢速率的一个主要原因。

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.