Increase in plasma propranolol caused by nicardipine is dependent on the delivery rate of propranolol

Abstract

The influence of a single oral dose of nicardipine 30 mg on the pharmacokinetics and pharmacodynamics of propranolol 80 mg given as a conventional release formulation and as a slow release formulation was studied in two separate groups of 12 healthy volunteers. Nicardipine doubled the area under the curve (AUC) and Cmax of propranolol when given as a conventional formulation, but increased it only slightly when given as a slow release formulation. This pharmacokinetic interaction did not result in clinically relevant changes in pharmacodynamic responses. These results indicate that the enhancement of the bioavailability of propranolol by coadministration of nicardipine is dependent on the delivery rate of propranolol, suggesting that the interaction is mainly due to shortterm haemodynamic effects of nicardipine leading to saturation of hepatic enzymes or functional shunting. Methods SubjectsSix healthy male volunteers (23-33 years, mean weight 75 kg) and six healthy female volunteers (24 35 years, mean weight 54 kg)