Physiological disposition of verapamil in man

Abstract

¹⁴C-D,L-verapamil was administered intravenously (lOmg) and orally (80 mg) to five volunteer patients. Plasma concentrations of verapamil, which were determined by mass fragmentography, declined bi-exponentially with half-lives of the α-phase ranging from 18 to 35 min and of the β-phase from 170 to 440 min. The apparent volume of distribution ranged from 270 to 460 litre and plasma clearance from 730 to 1980 ml/min. Following oral administration absorption was almost complete as judged from the area under the curve (AUC) of ¹⁴C-activity and cumulative urinary excretion of ¹⁴C. After intravenous infusion of verapamil about 80% of the radioactivity administered could be recovered in urine and faeces within 5 d. Despite its almost complete absorption after oral administration verapamil was shown to undergo extensive first pass metabolism as the bioavailability was only 10 to 22%. Rapid biotransformation had occurred as only a small percentage of AUC of ¹⁴C was seen to correspond to unchanged verapamil after both intravenous and oral administration.