title: Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.
abstract: 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, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) 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 AUC0-∞ 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 T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max 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 AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max 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.
authors.affiliation: Laboratory of Pharmacological and Toxicological Studies (LEFyT), Faculty of Veterinary Science, Universidad Nacional de La Plata , La Plata , Argentina.
authors.forename: Nora
authors.initials: N
authors.lastname: Mestorino
authors.affiliation: Laboratory of Pharmacological and Toxicological Studies (LEFyT), Faculty of Veterinary Science, Universidad Nacional de La Plata , La Plata , Argentina.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Marchetti
authors.affiliation: Laboratory of Pharmacological and Toxicological Studies (LEFyT), Faculty of Veterinary Science, Universidad Nacional de La Plata , La Plata , Argentina.
authors.forename: Mariana Florencia
authors.initials: MF
authors.lastname: Lucas
authors.affiliation: Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona , Barcelona , Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Modamio
authors.affiliation: Laboratory of Pharmacological and Toxicological Studies (LEFyT), Faculty of Veterinary Science, Universidad Nacional de La Plata , La Plata , Argentina.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zeinsteger
authors.affiliation: Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona , Barcelona , Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fernández Lastra
authors.affiliation: Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona , Barcelona , Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Segarra
authors.affiliation: Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona , Barcelona , Spain.
authors.forename: Eduardo Luis
authors.initials: EL
authors.lastname: Mariño
keywords: AUC; Cmax; Tmax; bioequivalence; bovines; oxytetracycline; pharmacokinetics