Prolongation of the PQ interval as a measure of therapeutic inequivalence between two formulations of diltiazem.

We studied the use of atrioventricular (AV) conduction time to assess the therapeutic equivalence of two diltiazem formulations in 20 volunteers in a double-blind, cross-over trial. ECG recording was carried out before and at several intervals after drug administration, and prolongation of the PQ interval (delta PQ) was taken as a pharmacodynamic response. In addition, diltiazem plasma concentrations were determined in 8 subjects. The effect of diltiazem increased proportionally with the plasma concentration and could be detected up to 10 h after administration. The area under the effect-time curve (AUEC(0-10)), the peak effect (Emax), and the effect mean residence time (MRTE) showed significant differences. In contrast to the pharmacodynamics, the pharmacokinetic profiles of diltiazem do not vary to the same extent. We conclude that the formulations are therapeutically different. Furthermore, at the administered dose, delta PQ appears to be a sensitive measure for assessing the electrophysiological properties of diltiazem.

RCT Entities:   Population Interventions Outcomes