Pharmacokinetic, haemodynamic and radionuclide studies with nicardipine in coronary artery disease

Abstract

Pharmacokinetic, haemodynamic and radionuclide studies explored the acute pharmacokinetic and pharmacodynamic actions of nicardipine in patients with coronary heart disease. Nicardipine infusion resulted in dose-related reductions in systolic and diastolic blood pressure and an increased heart rate. Pharmacodynamic activity was evident between 12 and 24 min following 5 and 10 mg i.v. nicardipine but by 3-6 min following the higher doses of 15 and 20 mg; hypotensive activity persisted for up to 2 h. Post-infusion nicardipine concentrations declined biexponentially; however the limited data precluded formal compartmental analysis. Plasma clearance ranged from 5-12 ml/min/kg, and appeared lower than previously reported volunteer data. The haemodynamic actions of nicardipine (10 mg infusion over 10 min) in 6 patients undergoing diagnostic catheterization were reductions in systolic, diastolic and mean systemic arterial pressure and systemic vascular resistance index. Heart rate and stroke volume index increased, and there was a small but statistically significant increase in pulmonary artery occluded pressure. Radionuclide parameters were measured in 20 patients with stable angina, at rest and during supine bicycle exercise, before and 3-5 min after nicardipine 10 mg intravenously. The left ventricular ejection fraction increased by 4% at rest but not during exercise. The left ventricular rest and exercise ejection and filling rates both increased with a concurrently reduced left ventricular ejection time. There was a highly significant inverse relationship between baseline exercise ejection fraction and the response to nicardipine; ejection fraction increased with low initial values but was either unchanged or fell with higher initial values.(ABSTRACT TRUNCATED AT 250 WORDS)

An exercise hemodynamic comparison of verapamil, diltiazem, and amlodipine in coronary artery disease

“…The heart rate, stroke volume, and cardiac index were augmented with a reduction in PAOP (during exercise); such changes probably reflect a reduced left ventricular afterioad with a possible contribution from the reversal of myocardial ischemia and regional or global improvement in ventricular function [26,27]. Our data on amlodipine are in agreement with other investigators' reports of dihydropyridine calciumchannel blocking agents in clinical practice.…”

Effects and interaction of nicardipine and volatile anesthetics in the rat heart-lung preparation

“…It appears to have little cardiodepressant action in the experimental animal [12], and has been shown to improve indices of cardiac performance in normal volunteers [13] and in patients with coronary artery disease [14,15]. Beneficial actions have also been described in acute myocardial infarction [16] and in chronic heart failure [17,18].…”

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

“…The plasma elimination half-life is short, being 4 to 5 hours [82], or even down to 35 to 110 minutes [85]. Intravenous nicardipine clearance rates are 0.3 to 0.9 1/hr/kg [83,86], with lower rates being found in patients with coronary artery disease [86]. Decreases in clearance rates with increasing doses of nicardipine suggest saturation of the hepatic mechanisms for the removal of the drug.…”