Abstract
A randomized, two-way, crossover, bioequivalence study in 32 fasting, healthy, male volunteers was conducted to compare two brands of clopidogrel 75 mg tablets, Thrombo (R) (EIPICO, Egypt) as test and Plavix (R) (Sanofi Pharma/Bristol-Myers Squibb, Paris, France) as reference. The study was performed in a Pharmaceutical Research Unit (PRU) using HPLC/ MS-MS. Arithmetic means for clopidogrel test versus reference formulation, respectively were for C-max (4.39 +/- 2.58 vs. 4.30 +/- 2.65) ng/ml, AUC(0-t) (11.98 +/- 9.82 vs. 12.01 +/- 9.46) ng.h/ml, AUC(0-infinity) (12.43 +/- 9.94 vs. 12.49 +/- 9.58) ng.h/ml, t(1/2) (6.06 +/- 3.87 vs. 5.87 +/- 2.47) h and the medians for t(max) (1 h vs. 0.75 11). Arithmetic means for clopidogrel carboxylic acid metabolite were C-max (3.75 +/- 1.19 vs. 3.51 +/- 0.97) mu g/ml AUC(0-t) (9.18 +/- 2.36 vs. 9.17 +/- 2.06) mu g.h/ml, AUC(0-infinity) (9.72 +/- 2.4 vs. 9.80 +/- 2.21) mu g.h/ml, and t(1/2) (6.43 +/- 3.52 vs. 6.33 +/- 1.71) h for test versus reference formulation respectively and there was no difference in the medians for t(max) (0.75 h). The parametric 90% confidence intervals for the mean of the difference between log-transformed values were within the accepted range for bioequivalence of 80 - 125% as proposed by the US-FDA, namely for clopidogrel (90.66% - 109.66%), (90.63% - 109.73%), and (93.19% - 115.37%) for AUC(0-t), AUC(0-infinity), and C-max, respectively and also for clopidogrel carboxylic acid metabolite (94.90 - 104.19), (94.04 - 103.86) and (96.47 - 114.79) for AUC(0-t), AUC(0-infinity), and C-max, respectively. Thus there was no significant difference between these values and therefore the two products can be considered bioequivalent.