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, Cmax, 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 (Tmax), 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 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 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ 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.
Highlights
The determination of the bioequivalence of veterinary drug formulations has become an increasingly important issue for both the European Union and the United States of America
European guideline affirms that “bioequivalence exists between veterinary medicinal products or between routes of administration if, under identical and appropriate experimental conditions, the bioavailability of the active ingredient differs within acceptable limits” [3]
The purpose of this study was to demonstrate the bioequivalence of two LA commercial OTCs, a test formulation (Cyamicin 20% LA) and the reference formulation (Terramycin 20% LA) after intramuscular administration to bovine
Summary
The determination of the bioequivalence of veterinary drug formulations has become an increasingly important issue for both the European Union and the United States of America. European guideline affirms that “bioequivalence exists between veterinary medicinal products or between routes of administration if, under identical and appropriate experimental conditions, the bioavailability of the active ingredient differs within acceptable limits” [3]. In other words, both definitions state that equivalent rate and extent of absorption will lead to same plasma drug concentration–time profiles and, essentially the same magnitude of therapeutic or toxic effects.
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