INCREASE IN PLASMA PROPRANOLOL CAUSED BY NICARDIPINE IS DEPENDENT ON THE DELIVERY RATE OF PROPRANOLOL

The influence of a single oral dose of nicardipine 30 mg on the pharma cokinetics and pharmacodynamics of propranolol 80 mg given as a conven tional release formulation and as a slow release formulation was studi ed in two separate groups of 12 healthy volunteers. Nicardipine double d the area under the curve (AUG) and C-max of propranolol when given a s a conventional formulation, but increased it only slightly when give n as a slow release formulation. This pharmacokinetic interaction did not result in clinically relevant changes in pharmacodynamic responses . These result's 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 mainl y due to shortterm haemodynamic effects of nicardipine leading to satu ration of hepatic enzymes or functional shunting.