Systemic availability of oral verapamil and effect on PR interval in man

1 The plasma levels of verapamil and its major metabolite norverapamil were related to its effect as a Ca-antagonist on atrio-ventricular (AV) conduction, judged from prolongation of the PR interval in six normal volunteers. 2 Intravenous administration (0.1 mg kg-1) was compared to oral administration (120 mg) in each subject. 3 Intravenous verapamil showed a mean distribution half-life (alpha) of 8.5 min and elimination half-life (beta) of 2.0 h. The volume of distribution was about 112.1. Oral dosage gave an elimination half-life of 2.7 h, and a norverapamil half-life which averaged 4.6 h. The bioavailability of the oral dose averaged 22% (17 to 29%). 4 After the oral dose the percentage change in PR interval in the five appropriate subjects correlated significantly with the log plasma verapamil level (r = 0.732), but not with the log plasma norverapamil level (r = 0.078); norverapamil could not be detected after the intravenous dose. One subject developed Wenckebach type second degree AV block after each dose.