Pharmacokinetics of verapamil from an osmotic system with delayed onset

Three formulations of an osmotic system of verapamil [GITS (verapamil)] were studied in two groups of subjects. Two formulations had a 2-fold difference in release rates and were compared in the first group. In the second group, a third formulation with release rate similar to the second formulation but with a longer delay was studied following single and multiple administrations. Drug doses were administered in the evening ; serial blood samples were collected. Study objectives were i) to compare the effect of release rates on the relative bioavailability of verapamil and ii) to establish an in vitro and in vivo correlation for the release rate. Doubling the release rate led to an increase in the bioavailability of R- and S-verapamil not associated with a reduction in verapamil metabolism to norverapamil. The in vivo absorption and in vitro release rate profiles paralleled each other for all three formulations, establishing an in vivo and in vitro correlation.