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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 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.

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Mikus, G., Zekorn, C., Brecht, T. et al. Acute haemodynamic effects of i.v. nitrendipine in healthy subjects. Eur J Clin Pharmacol 41, 99–103 (1991). https://doi.org/10.1007/BF00265899

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Key words

  • Nitrendipine
  • i.v. infusion
  • serum concentrations
  • haemodynamic effects
  • protein binding
  • healthy subjects
  • polyethylene glycol
  • ethanol