Influence of cimetidine on verapamil kinetics and dynamics

The kinetics and dynamics of single doses of verapamil (10 mg iv and 120 mg by mouth) were followed in eight subjects on oral cimetidine (300 mg every 6 hr) and placebo. Cimetidine had no effect on intravenous verapamil kinetics but induced a significant rise in oral verapamil bioavailability. Other kinetic parameters of verapamil were not altered by cimetidine. Verapamil induced a significant slowing of atrioventricular conduction (39.8 msec intravenous; 24.5 msec oral). Although there was a significant increase in oral verapamil bioavailability, after cimetidine, there was no change in PR interval prolongation with either oral or intravenous verapamil. Our data demonstrate the importance of correlating measurable drug effects with kinetic studies when drug interactions are studied and their clinical significance is assessed.