Average bioequivalence of two oral formulations of ticlopidine in healthy volunteers

Objective: The aim of the study was to describe the pharmacokinetic properties and compare the rate and extent of absorption of ticlopidine from a new generic tablet formulation compared. with the reference formulation. Methods: In this single-dose, open-label, e-sequence, 2-period, randomized crossover study, all 24 subjects received one 250-mg dose of ticlopidine. Subjects were assigned to treatment sequences in groups of 4 by block randomization. They fasted from 10 hours before until 5 hours after administration of the medication. Venous blood samples were taken before each administration and at 14 different times within 48 hours after administration, and plasma concentrations of ticlopidine were determined by high-performance liquid chromatography. Clinical adverse events were recorded after an open-ended question and a symptom checklist during the study. For the purpose of bioequivalence analysis, area under the plasma concentration-time curve from zero to infinity (AUC(o-infinity)) and maximum concentration (C-max) were considered as the primary variables and time to C-max (T-max) as the secondary variable. C-max and T-max were obtained directly from plasma data, the elimination constant was estimated by log-linear regression, and AUC was calculated by the trapezoidal rule. AUC and C-max were tested for bioequivalence after log-transformation of data. Results: The 90% standard CIs of the mean values for the test/reference ratios were 0.80 to 1.10 for AUC and 0.87 to 1.17 for C-max. The point estimate was 92.7% for AUC and 102% for C-max. No significant period effects were obtained. Mean T-max was 1.9 hours for the test formulation (range, 0.5 to 3.0 hours) and 2.5 hours for the reference formulation (range, 1.0 to 4.0 hours). Conclusions: Our results are within the acceptable bioequivalence range of 0.80 to 1.25. We conclude that the 2 formulations are bioequivalent and, therefore, interchangeable.