Bioequivalence of two amoxicillin-potassium clavulanate oral preparations in dogs

The aim of this trial was to carry out a bioequivalence (BE) study in dogs using a generic preparation of amoxicillin-potassium clavulanate vs a commercially available reference preparation, both claiming to achieve plasma concentrations that allow a 12 h dosing interval after oral administration. The oral pharmacokinetic profiles of a single dose of each preparation were carried out in 12 adult mongrel dogs in a crossover model with a 10 day washout period at a dose of 12.5 mg/kg of trihydrate amoxicillin and potassium clavulanate as tablets. A composite determination of amoxicillin-potassium clavulanate concentration in each sample of plasma was carried out in triplicate, using a microbiological agar diffusion analysis. Pharmacokinetic analysis was carried out with a non-compartmental model. Statistical analysis of pharmacokinetic variables was carried out by ANOVA and Bonferroni t test, setting a P < 0.05. In accordance with international standards, it was found that the generic preparation failed to be bioequivalent, i.e: AUCO-infinity 9.08 +/- 0.26 mu g h/ml and Cmax 5.48 +/- 0.19 mu g/ml for the generic preparation vs AUCO-infinity 13.28 +/- 0. 30 mu g h/ml and Cmax 2.9 +/- 0.17 mu g/ml for the reference one. A 0.25 mu g/ml breakpoint can be set as minimum effective plasma concentration for amoxicillin; hence the generic preparation requires a dose interval of eight h.