MODULATION OF THE HAEMODYNAMIC AND ELECTROCARDIOGRAPHIC EFFECTS OF NIFEDIPINE BY A CYTOCHROME P-450 ENZYME INHIBITOR

Abstract

The effects of a single dose of nifedipine (5 mg/Kg, 1.P.) alone, Cimetidine (25 mg/Kg, I.P. for 7 days) alone or their combination on the arterial blood presure, heart rate, the calculated double product, and electrocardiogram (ECG) in anaesthetized normotensive rats have been studied. Results of the present investigation showed that nifedipine, cimetidine or their combination didn't affect the heart rate. The administration of nifedipine alone produced a significant reduction in arterial blood pressure after 15 min., This effect lasted for 90 min after administration (recording 30% of the initial value). On the other hand, the administration of nifedipine to rats pretreated with cimetidine produced more significant and prolonged reduction in arterial blood pressure, this effect remained to the end of experiment (180 min.). moreover, nifedipine alone produced significant prolongation of PR-and QT intervals. While nifedipine administartion to the rats pretreated with cimetidine produced a significant and continuous prolongation of the PR-interval as well as QT interval and also produced an increase in T-wave amplitude and duration. Cimetidine did not alter any of ECG parameters. The results of the present study showed that cimetidine potentiates the action of nifedipine on blood pressure and support and extend the previous reports in several models that, cimetidine increases the plasma concentration and consequently the bioavailability of nifedipine due to its characteristic ability to inhibit the liver microsomal enzyme cytochrome P-450.