Pharmacokinetics and bioequivalence study of two cetirizine hydrochloride formulations in healthy Chinese male volunteers.

The pharmacokinetics and relative bioavailability/bioequivalence of two formulations of cetirizine hydrochloride (CAS 83881-51-0) were assessed in this paper. Using a two-treatment, two-period, two-sequence, randomized crossover design, test and reference formulations were administered as individual single doses to 18 Chinese healthy male volunteers under non-fed conditions, with a 7-day washout period between dosing. Fourteen blood samples were drawn from each subject over a 34-h period. Cetirizine concentrations in plasma were determined by a validated high performance liquid chromatographic-ultraviolet (HPLC/UV) assay, and pharmacokinetic parameters, Cmax, AUC(0-t), AUC(0-infinity) and t1/2 were calculated from the plasma concentration-time data of each individual and during each period by applying non-compartmental analysis. Pharmacokinetic data for test and reference formulations were analyzed statistically to test for bioequivalence of the two formulations. After oral administration the values of Cmax, tmax, t1/2, MRT, AUC(0-t), AUC(0-infinity) for test and reference formulations were 0.80 +/- 0.14 and 0.80 +/- 0.23 microg/ml, 0.8 +/- 0.4 and 1.1 +/- 0.7 h, 7.59 +/- 0.68 and 7.63 +/- 0.93 h, 10.59 +/- 0.94 and 10.92 +/- 1.26 h, 6.00 +/- 1.04 and 5.98 +/- 1.39 microg x h/ml, respectively. ANOVA and CI test showed no significant (p > 0.05) variation in these pharmacokinetic parameters of test and reference formulations. When the AUC(0-t) values for both formulations for natural log-transformed data were compared, the test formulation showed a bioavailability of 100.9 +/- 7.7%, as compared to the reference formulation. These values are within the acceptance limit of 80-125%. No adverse events were observed in any of the subjects during the two runs of the study. Both clinical and laboratory parameters of all subjects showed no clinically significant changes. This study shows that both formulations were well tolerated and the test formulation can be considered a pharmaceutically and therapeutically equivalent alternative to the reference formulation.