ISSN:
1432-1041
Keywords:
Nitrendipine
;
i.v. infusion
;
serum concentrations
;
haemodynamic effects
;
protein binding
;
healthy subjects
;
polyethylene glycol
;
ethanol
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00265899
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