Influence of cimetidine on verapamil kinetics and dynamics

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Abstract
The kinetics and dyanmics of single verapamil doses (10 mg i.v. and 120 mg oral) were followed in 8 subjects on oral cimetidine (300 mg every 6 h) and placebo. Cimetidine had no effect on i.v. verapamil kinetics but induced a significant rise in oral verapamil bioavailability. Other verapamil kinetic parameters were not altered by cimetidine. Verapamil induced a significant atrioventricular conduction slowing (39.8 ms i.v.; 24.5 ms oral). Although there was a significant increase in oral verapamil bioavailability after cimetidine, there was no change in peripheral resistance interval prolongation with either oral or i.v. verapamil. The importance of correlating measurable drug effects with kinetic studies, when drug interactions are studied and their clinical significance is assessed, was demonstrated.