Plasma concentrations and hemodynamic effects of nifedipine: a study in anesthetized dogs

The elimination kinetics of the calcium channel blocking agent nifedipine were studied in three male mongrel dogs after single intravenous bolus doses, and the drug's disposition followed first-order kinetics. After single intravenous doses, the elimination rate constant (mean +/- SE) was 0.693 +/- 0.069 h-1; the total body clearance, 0.736 +/- 0.226 L/h/kg; and the apparent volume of distribution, 1.15 +/- 0.12 L/kg. Based on these data, a model for the administration of nifedipine by an intravenous bolus-infusion regimen was developed to rapidly achieve and maintain stable plasma drug concentrations. Testing of this model in six anesthetized, open-chest dogs revealed pulmonary artery (mixed venous) drug concentrations that were consistently lower than those predicted, with stable plasma nifedipine levels achieved within 5 min and maintained over 60-min study periods. In these animals, a linear relationship was found between nifedipine concentrations in plasma and the total amount of drug administered (r = 0.92, p less than 0.001). Log-linear relationships were found between plasma nifedipine concentrations and mean arterial blood pressure (r = -0.93, p less than 0.001), cardiac output (r = 0.94, p less than 0.001), peripheral vascular resistance (r = -0.93, p less than 0.001), and pulmonary vascular resistance (r = -0.83, p less than 0.001). In addition, infusion of CaCl2 (3 mg/kg/min) resulted in increases in blood pressure despite the presence of stable plasma nifedipine concentrations. No electrocardiographic changes were seen at any plasma nifedipine level.