Bioequivalence of two oral formulations of clopidogrel tablets in healthy male volunteers.
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 (EIPICO, Egypt) as test and Plavix (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 Cmax (4.39 +/- 2.58 vs. 4.30 +/- 2.65) ng/ml, AUC0-t (11.98 +/- 9.82 vs. 12.01 +/- 9.46) ng.h/ml, AUC0- yen (12.43 +/- 9.94 vs. 12.49 +/- 9.58) ng.h/ml, t1/2 (6.06 +/- 3.87 vs. 5.87 +/- 2.47) h and the medians for tmax (1 h vs. 0.75 h). Arithmetic means for clopidogrel carboxylic acid metabolite were Cmax (3.75 +/- 1.19 vs. 3.51 +/- 0.97) microg/ml AUC0-t (9.18 +/- 2.36 vs. 9.17 +/- 2.06) microg.h/ml, AUC0- yen (9.72 +/- 2.4 vs. 9.80 +/- 2.21) microg.h/ml , and t1/2 (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 tmax (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 AUC0-t, AUC0- yen, and Cmax, respectively and also for clopidogrel carboxylic acid metabolite (94.90 - 104.19) , (94.04 - 103.86) and (96.47 - 114.79) for AUC0-t , AUC0- yen, and Cmax, respectively. Thus there was no significant difference between these values and therefore the two products can be considered bioequivalent.
El Ahmady
O
O
Egyptian International Pharmaceutical Industries Company, Cairo, Egypt.
Ibrahim
M
M
Hussein
A M
AM
Bustami
R T
RT
D000284:Administration, Oral; D000328:Adult; D000077144:Clopidogrel; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D010975:Platelet Aggregation Inhibitors; D013607:Tablets; D000077144:Clopidogrel; D013988:Ticlopidine