Acute haemodynamic effects of i.v. nitrendipine in healthy subjects.
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.
Mikus
G
G
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
Zekorn
C
C
Brecht
T
T
Eichelbaum
M
M
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007866:Leg / Q000098:blood supply; D008954:Models, Biological; D009568:Nitrendipine / Q000494:pharmacology*; D011485:Protein Binding; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D009568:Nitrendipine