Acute haemodynamic effects of i.v. nitrendipine in healthy subjects

Eur J Clin Pharmacol. 1991;41(2):99-103. doi: 10.1007/BF00265899.

Abstract

The haemodynamic effects of an i.v. infusion of 2 mg nitrendipine have been studied in six healthy volunteers. Nitrendipine significantly decreased the systolic (-8.3%) diastolic (-19.9%) and mean arterial (-11.6%) blood pressures and the peripheral vascular resistance (-57.8%), and significantly increased leg blood flow (+128%). Stroke volume did not change. Due to the increase in heart rate (+28.5%), the cardiac output (2.8.2%) rose significantly. The haemodynamic effects were closely related to the serum nitrendipine concentration. The sigmoidal Emax-model was appropriate to describe the data. Pronounced interindividual differences in the serum nitrendipine concentrations required to elicit 50% of the maximum haemodynamic effect (EC50) were observed. The EC50 for the increase in leg blood flow ranged from 2.9 to 30.9 ng/ml and for the reduction in peripheral vascular resistance from 2.1 to 25.7 ng/ml. Interindividual differences in EC50 values were less pronounced if based on unbound serum nitrendipine levels. The fraction of nitrendipine not bound to serum proteins showed a three-fold difference between subjects, with free fractions ranging from 0.011 to 0.036. The unbound EC50 values for the increase in leg blood flow varied between 0.06 and 0.44 ng/ml and for the reduction in peripheral vascular resistance from 0.07 to 0.35 ng/ml. Based on the serum concentrations associated with comparable haemodynamic effects nitrendipine was at least three-times more potent than nifedipine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Infusions, Intravenous
  • Leg / blood supply
  • Models, Biological
  • Nitrendipine / pharmacology*
  • Protein Binding
  • Reference Values
  • Regional Blood Flow / drug effects
  • Time Factors
  • Vascular Resistance / drug effects

Substances

  • Nitrendipine