PHARMACOKINETIC INTERACTION BETWEEN NIFEDIPINE AND PROPRANOLOL

Summary— In 8 healthy volunteers, single‐dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol. An elevation of the mean C_max was found, from 73.9±14.1 when nifedipine was taken alone, to 115.7±12.1 (SE) ng/ml (P<0.02) when the agent was combined with propranolol. The AUC^0‐∞ increased as well, from 287.1±33.5 to 363.0±54.3 (SE) (μg.hr)/1 (P<0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half‐life (α or β phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects. The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic ± first‐pass ± clearance, as a result of changes in hepatic blood flow. 1988 Société Française de Pharmacologie et de Thérapeutique