AUTHOR=Mestorino Nora , Marchetti María Laura , Lucas Mariana Florencia , Modamio Pilar , Zeinsteger Pedro , Fernández Lastra Cecilia , Segarra Ignacio , Mariño Eduardo Luis 

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

JOURNAL=Frontiers in Veterinary Science

VOLUME=3

YEAR=2016

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2016.00050

DOI=10.3389/fvets.2016.00050

ISSN=2297-1769

ABSTRACT=<p>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 μg/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, <italic>C</italic><sub>max</sub>, and the area under the concentration-versus-time curve extrapolated to infinity, AUC<sub>0–∞</sub>) of both products. In the case of the time to maximum concentration (<italic>T</italic><sub>max</sub>), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC<sub>0–∞</sub> values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the <italic>T</italic><sub>max</sub> (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean <italic>C</italic><sub>max</sub> some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC<sub>0–∞</sub> and <italic>T</italic><sub>max</sub> values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of <italic>C</italic><sub>max</sub> falls outside the proposed interval. It was concluded that <italic>C</italic><sub>max</sub> 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.</p>