Average bioequivalence of two oral formulations of ticlopidine in healthy volunteers

Objective: The aim of the study was to describe the pharmacokinetic propert ies 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. S ubjects were assigned to treatment sequences in groups of 4 by block random ization. They fasted from 10 hours before until 5 hours after administratio n of the medication. Venous blood samples were taken before each administra tion and at 14 different times within 48 hours after administration, and pl asma concentrations of ticlopidine were determined by high-performance liqu id chromatography. Clinical adverse events were recorded after an open-ende d question and a symptom checklist during the study. For the purpose of bio equivalence analysis, area under the plasma concentration-time curve from z ero to infinity (AUC(o-infinity)) and maximum concentration (C-max) were co nsidered as the primary variables and time to C-max (T-max) as the secondar y variable. C-max and T-max were obtained directly from plasma data, the el imination constant was estimated by log-linear regression, and AUC was calc ulated by the trapezoidal rule. AUC and C-max were tested for bioequivalenc e after log-transformation of data. Results: The 90% standard CIs of the mean values for the test/reference rat ios were 0.80 to 1.10 for AUC and 0.87 to 1.17 for C-max. The point estimat e 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 h ours). Conclusions: Our results are within the acceptable bioequivalence range of 0.80 to 1.25. We conclude that the 2 formulations are bioequivalent and, th erefore, interchangeable.