BIOEQUIVALENCE STUDY OF 2 SLOW-RELEASE DILTIAZEM FORMULATIONS USING DYNAMIC MEASURES IN HEALTHY-VOLUNTEERS

The bioequivalence of two slow-release diltiazem formulations [formula tion A (Cardizem(R), Marion Merrell Dow) and formulation B (Dilter(R), Natco Pharma)] was investigated in 12 healthy volunteers in a double- blind crossover study. Atrioventricular conduction time (PQ interval) was taken as a pharmacodynamic response to assess bioequivalence. An E CG recording was carried out before and at various time intervals afte r drug administration and PQ interval was measured. The mean PQ interv al before administration of either formulation was similar. There was significant prolongation of the PQ interval from the second hour onwar ds with the two formulations. With Dilter(R), mean maximum PQ interval (E-max) was 0.2 +/- 0.03 msec, peak time (t(max)) was 2.67 +/- 0.98 h ours and area under the effect-time curve (AUC) was 4.18 +/- 0.47 msec h. With Cardizem(R), the mean values were 0.2 +/- 0.04 msec, 2.83 +/- 1.03 hours and 4.23 +/- 0.4 msec . h for E-max, t(max) and AUC, respe ctively. Both formulations produced similar decreases in systolic and diastolic blood pressures and heart rate. All pharmacodynamic variable s used to assess the bioequivalence of the two formulations were found to be comparable. The estimate of the rate and extent of the effect o n PQ interval and the AUC suggested that both formulations were bioequ ivalent.