title: The pharmacology of verapamil. I. Elimination kinetics in dogs and correlation of plasma levels with effect on the eletrocardiogram.
abstract: 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.
mesh_terms: D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology
chemical_list: D014700:Verapamil