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  • Title: The pharmacology of verapamil. IV. Kinetic and dynamic effects after single intravenous and oral doses.
    Author: McAllister RG, Kirsten EB.
    Journal: Clin Pharmacol Ther; 1982 Apr; 31(4):418-26. PubMed ID: 7060323.
    Abstract:
    Kinetics and plasma level-effect correlates for verapamil were studied in 20 normal young men (mean age, 25.2 +/- 3.6 yr). In a randomized four-way crossover design, each subject received 10 mg verapamil intravenously and 80, 120, and 160 mg in single oral doses. Changes in heart rate, blood pressure, and PR interval were evaluated serially after each dose; plasma concentrations of verapamil were measured by high-performance liquid chromatography. Levels of the active metabolite norverapamil were determined in five subjects. Verapamil kinetics were the same after intravenous and oral doses: elimination half-life (t 1/2 beta) ranged from 3.7 to 4.8 hr, apparent volume of distribution varied between 4.2 and 5.5 l/kg, and total clearance was 0.71 to 0.86 l/hr/kg. Verapamil bioavailability was not dose dependent and averaged 19.4%. Norverapamil, found only after oral doses, had a t 2/2 beta and maximum concentration much the same as the parent drug. There were only minor effects on heart rate and blood pressure after single doses. Hysteresis analysis showed that plasma verapamil concentrations after intravenous doses correlated with PR interval prolongation only after a 30-min lag time; there was no lag after oral doses. There was considerable interindividual variation in sensitivity to verapamil's effect on atrioventricular conduction; subjects with longer control PR interval values tended to have greater prolongation of effect than those with shorter intervals. Verapamil was well tolerated in both dosage forms by all subjects.
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