Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 mu g/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C-max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC(0-infinity)) of both products. In the case of the time to maximum concentration (T-max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC(0-infinity) values did not reveal any significant differences (311.40 +/- 93.05 mu g h/mL and 287.71 +/- 45.31 mu g h/mL, respectively). The results were similar for the Tmax (3.58 +/- 0.90 h versus 3.42 +/- 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 +/- 3.66 mu g/mL and 10.43 +/- 3.84 mu g/mL, respectively). The 90% confidence intervals for the ratio of AUC(0-infinity) and Tmax values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation.