ENZYME KINETICS OF NICARDIPINE METABOLISM IN HUMAN LIVER MICROSOMES

AIM To study the enzyme kinetics of nicardipine metabolism and the effects of selective CYP450 inhibitors on the metabolism of nicardipine in human liver microsomes. METHODS Human liver microsomes were used to perform enzyme kinetic studies. Various selective CYP inhibitors were used to investigate their inhibitory effects on the metabolism of nicardipine and the principal CYP isoform involved in dehydrogenation of nicardipine dihydropyridine ring. RESULTS The dehydrogenation of nicardipine was significantly inhibited by Ketoconazole. High level diethyldithiocarbamate was also shown to inhibit the above metabolism. While phenacetin, quinidine, sulfaphenazole and tranylcypromine showed little inhibitory effect on the dehydrogenation of nicardipine. CONCLUSION CYP3A was shown to be involved in nicardipine metabolism. CYP3A inhibitors and nicardipine may interact metabolicly, thereby reducing the rate of nicardipine metabolism.