Bioequivalence study of rofecoxib tablets.

The study was designed to evaluate the bioavailability of two rofecoxib (CAS 162011-90-7) tablet formulations. Twenty-four healthy male volunteers were administered a 25 mg tablet of the test formulation (Ecrox) containing rofecoxib or the originator product (reference). The trial was performed according to an open, cross-over design with a wash-out period of 7 days. Blood samples were taken up to 72 h post dose, the plasma was separated and the concentrations of rofecoxib were determined by an HPLC method. The mean Cmax were 192.07 ng/mL and 187.35 ng/mL, while the mean AUC0-t were 3613.84 ng x h/mL and 3501.56 ng x h/mL for the test and reference formulations, respectively. The median tmax was 3.75 h for the test tablet and 4.00 h for the reference formulation. The mean t(1/2 el) was 10.66 h and 10.61 h for the test and reference formulation, respectively. Mean MRT values for the test and reference tablets were 15.34 h and 15.33 h, respectively. Mean MRT values for the test and reference tablets were 15.34 h and 15.33 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence interval for the primary target parameters, i.e. intra-individual ratios of AUC0-t and Cmax of rofecoxib were between 0.99 and 1.10 (AUC0-t) as well as between 0.96 and 1.10 (Cmax) and thus within the acceptance ranges. Concerning the secondary parameter tmax the 90% confidence interval for the intra-individual differences was between -0.25 and 0.25 h. In the light of the present study it can be concluded that the two evaluated rofecoxib formulations, i.e. test tablets of rofecoxib and a reference preparation are bioequivalent in terms of the rate and extent of absorption.