The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration

Abstract

The pharmacokinetics of verapamil were determined in 8 normal male subjects (age range, 24-28 years) after administration of 0.2 mg/kg over a 3-4 min period. Plasma drug concentrations were measured by a gas-chromatographic method using a nitrogen-specific detector with a sensitivity of 5 ng/ml. Verapamil levels fell in a biexponential pattern, and the data were fitted to a two-compartment model with the NONLIN computer program. The distribution phase half-life was 3.51 min and that of the elimination phase, 110.5 min; the volume of distribution was 178 +/- 26 liters, and the plasma clearance ws 1.06 +/- 0.27 liters/min. The P-R interval of the surface electrocardiogram was increased in each subject in direct proportion to the verapamil plasma level, but with considerable between-subject variability. One subject developed transient Mobitz I block at a plasma drug concentration of 162 ng/ml. At peak verapamil concentrations, mean T-wave amplitude decreased 35 +/- 11% from control height. The results of this study suggest that P-R interval prolongation can be used as an indication of verapamil effect in patients with sinus rhythm.