The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes.

The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.