Noninvasive assessment of the haemodynamic effects of nicardipine in normotensive subjects.

Calcium antagonists reduce myocardial contractility in vitro. Nicardipine is a dihydropyridine derivative with enhanced selectivity for vascular smooth muscle. We have studied the pharmacokinetics and the haemodynamic effects that occur in man following bolus intravenous administration of nicardipine. Ten normotensive male subjects received either nicardipine or placebo i.v., allocated in a randomised double-blind manner, over 60s. Plasma nicardipine concentration, blood pressure, heart rate, and systolic time intervals were measured before dosing and at frequent intervals between 1 and 360 min post dosing. At 160 micrograms kg-1, adequate plasma levels of nicardipine were obtained to permit analysis of individual pharmacokinetic variables, and significant and consistent haemodynamic effects were seen. After injection of nicardipine, systolic BP and the QS2 (measure of total electromechanical systole) and QT intervals were not altered. The changes in BP and heart rate were consistent with arteriolar vasodilatation. The changes in PEP and LVET suggest an increase in cardiac contractility, which is unlikely to be a direct effect of nicardipine on the myocardium but rather a result of afterload reduction. The close correlation of nicardipine plasma level with haemodynamic effect should permit accurate dose titration. The net increase in contractility should allow nicardipine to be administered safely with beta-adrenoceptor blocking drugs.