Prolongation of verapamil elimination kinetics during chronic oral administration

The elimination of verapamil and its n-demethylated metabolite, norverapamil, was studied in nine patients with chronic atrial fibrillation after the first oral verapamil dose and during chronic oral verapamil administration. Significant increases (p less than 0.01) were seen in the elimination half-lives (t 1/2's) of both verapamil (6.4 +/- 3.5 to 12 +/- 5 hours, mean +/- SD) and norverapamil (10.3 +/- 6 to 16.5 +/- 7 hours) during chronic oral verapamil administration. These pharmacokinetic observations have important clinical implications for the rational long-term administration of this agent. Once steady-state serum concentrations have been achieved during chronic verapamil administration, verapamil doses should be given at less frequent intervals or in smaller doses in order to produce the desired serum concentration and therapeutic response and to minimize unwanted or toxic drug effects.