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

Summary 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 E_max-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.