Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment

Intravenous nicardipine, 5 mg, was administered in two comparable groups of eight patients with chronic coronary artery disease but no clinical signs of heart failure. One group had received no previous treatment and served as a control group, and the other had received long-term treatment with large oral doses of propranolol. Blood concentrations of nicardipine were higher, and the area under the plasma concentration curve was greater in the group previously treated by propranolol. The total clearance of nicardipine was decreased in patients taking propranolol, without a change in the half-life of the drug. Typical hemodynamic responses, namely, a decrease in aortic pressure and in arterial resistances, were greater and more lasting in patients previously treated orally by propranolol. Filling pressure remained stable in both groups. The nicardipine infusion did not induce signs of dromotropic or inotropic negative effects in either group. The greater and more lasting hemodynamic effects of nicardipine in the group previously treated orally by propranolol do not seem to be related to an overall hemodynamic action of propranolol, but are probably due to higher nicardipine plasma levels, and may be caused by a decrease in hepatic blood flow induced by propranolol, with a consequent decrease in nicardipine clearance and by a smaller nicardipine volume of distribution in the propranolol group.