Bioequivalence study of clopidogrel bisulfate film-coated tablets.

The aim of the present study was to evaluate the bioequivalence of two clopidogrel (CAS 120202-66-6) formulations. The study was performed according to an open, cross-over design in one study center in 36 healthy male and female volunteers, comparing a new generic product (tablets containing clopidogrel bisulfate, 75 mg) with the originator product (reference). In each of the two study periods (separated by a wash-out of 7 days) a single dose of 150 mg (test or reference) was administered. Blood samples were taken up to 48 h post dose, the plasma was separated and the concentrations of clopidogrel were determined by an LC/MS/MS method. AUC0-inf, AUC0-t, Cmax, Tmax and T(1/2 el) were calculated for both formulations. The mean AUC0-inf, AUC0-t and Cmax were 29.94 ng x h/mL, 29.53 ng x h/mL and 7.386 ng/mL, respectively, for the test formulation and 29.24 ng x h/mL, 28.83 ng x h/mL and 7.921 ng/mL, respectively, for the reference formulation. The median Tmax for both formulations was 1.25 h. The point estimators of the ratios test/reference formulation for AUC0-inf, AUC0-t and Cmax were 101.17%, 101.13% and 90.96%, respectively. Furthermore, the 90% geometric confidence intervals of the mean ratio of In-transformed AUC0-inf and AUC0-t were narrow and symmetrical around 100%, i.e. from 96.38% to 106.21% for AUC0-inf and from 96.20% to 106.30% for AUC0-t, whereas the confidence interval for Cmax was 84.07% to 98.41%. In can be concluded that the two clopidogrel formulations (test formulation of clopidogrel bisulfate and reference formulation) are bioequivalent in terms of the rate and extent of absorption.