title: Plasma concentrations and hemodynamic effects of nifedipine: a study in anesthetized dogs.
abstract: 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.
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D009543:Nifedipine; D002122:Calcium Chloride