The pharmacology of verapamil. I. Elimination kinetics in dogs and correlation of plasma levels with effect on the eletrocardiogram
McAllister, R.G.; Bourne, D.W.; Dittert, L.W.
Journal of Pharmacology and Experimental Therapeutics 202(1): 38-44
1977
ISSN/ISBN: 0022-3565 PMID: 874818 Document Number: 120318
The elimination kinetics of verapamil, an experimental antiarrhythmic agent which inhibits slow-channel activity, have been studied in mongrel dogs after i.v. drug administration. The disposition of verapamil follows first-order kinetics and may be adequately described by a one-compartment model. After single i.v. doses of the drug, the overall elimination rate constant (mean +/-S.E.M.) was 0.0146 +/- 0.0021 min-1; the apparent volume of distribution was 4.47 +/- 0.40 liters/kg; and the total body drug clearance was 1244 +/- 113.4 ml/min. After longer i.v. infusions, the disposition kinetics were similar to those found with bolus dosing. A linear relationship was found between verapamil plasma concentrations and changes in atrioventricular conduction time, as estimated from the P-R interval of the surface electrocardiogram (r = 0.95, P less than .001). No changes were seen in the QRS duration of Q-T interval. These data show that the effect of verapamil of verapamil on slow-channel-dependent conduction in the heart is directly related to the concentration of the drug in plasma.