Verapamil disposition and effect on PQ-intervals after buccal, oral and intravenous administration

The absorption, pharmacokinetics and effect on PQ-intervals of verapamil (Isoptin) administered as buccal tablet (20 mg), oral capsule (80-120 mg) and as an intravenous injection (5 mg) have been determined in 7 healthy subjects. Hysteresis plots of the percentage change in PQ-interval and serum concentration indicate that the efficacy of verapamil after buccal and intravenous application, as in earlier findings with sublingual verapamil tablets, was higher than after oral application. Thus the serum concentration-response curve after oral application is displaced towards the right reflecting lower potency. This phenomenon has been attributed by other workers to a stereospecific metabolism of the more active L-isomer during first pass through the liver, but competition at the receptor with metabolites cannot yet be ruled out. The rate of absorption, T1/2(alpha), terminal elimination half-life T1/2(gamma), and tmax of the buccal tablet was not significantly different from the oral capsule. The absolute bioavailability of the buccal preparation (37%) was slightly greater than the oral capsule (33%) and both had higher bioavailability than observed in earlier studies on verapamil dragees (10-20%). Thus, although the buccal tablet was alkalinised and had a rapid disintegration in vitro, characteristics thought to increase buccal uptake, the bioavailability is still much less then 100%.