Abstract
In 8 healthy volunteers, single-dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol. An elevation of the mean Cmax was found, from 73.9 +/- 14.1 when nifedipine was taken alone, to 115.7 +/- 12.1 (SE) ng/ml (P less than 0.02) when the agent was combined with propranolol. The AUC0----infinity increased as well, from 287.1 +/- 33.5 to 363.0 +/- 54.3 (SE) (micrograms.hr)/l (P less than 0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half-life (alpha or beta 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.
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