Sustained-release verapamil: multiple-dose pharmacokinetic comparison of 120-mg and 240-mg tablets and the effect of halving a 240-mg tablet.

Ten healthy male volunteers, aged 18-37 years, entered a balanced crossover comparison of the pharmacokinetic profiles of (a) one 240 mg verapamil HCl sustained-release tablet (Isoptin SR 240, Securon SR) (1 X 240 mg) and (b) either: two half 240-mg verapamil HCl sustained-release tablets (2 X half 240-mg tablets, Study 1) or two 120-mg verapamil HCl sustained-release tablets (Isoptin SR 120) (2 X 120 mg, Study 2). Each phase of the two studies consisted of once-daily administration of verapamil for 8 days with a 1-week washout period between phases. Plasma samples were collected for 24 h after dosing on day 8 of each phase and assayed for verapamil and norverapamil by high-performance liquid chromatography. In both studies there were no significant differences between the mean Cmax, Tmax, and area under curve values observed after the two treatments. There were no significant differences between mean verapamil plasma concentrations at any time during the dose interval. The mean bioavailability of the 120-mg tablet relative to the 240-mg tablet was 107%, with 95% confidence limits of 81 and 142%, indicating that the amount of verapamil available from the two tablets was similar. This investigation indicates that both tablet sizes appear to have similar sustained-release properties and that the formulation retains its sustained-release properties when the tablet is broken.