Relative Oral Bioavailability of Two Amoxicillin-Clavulanic Acid Formulations in Healthy Dogs: A Pilot Study

The use of human generic amoxicillin-clavulanic acid formulations in veterinary medicine is currently lacking supportive evidence. This pilot study was conducted to determine preliminary pharmacokinetic parameters and relative oral bioavailability of a human generic and veterinary proprietary 4:1 amoxicillin-clavulanic acid formulation in healthy dogs to evaluate whether drug exposure was similar and to determine if further comparative investigation is warranted. Each dog received a single oral dose of each formulation containing 500:125 mg of amoxicillin-clavulanic acid at two separate instances with a 2 wk washout period between product administration. Following drug administration, blood was collected at fixed times over 24 hr to measure plasma amoxicillin and clavulanic acid concentrations using liquid chromatography-mass spectrometry. There were no statistically significant differences between pharmacokinetic parameters of either formulation. Clavulanic acid showed greater between-dog variation in drug exposure between formulations compared with amoxicillin and was also observed to be more variable within the veterinary proprietary formulation. The average relative oral bioavailability was 98.2% (23.6% coefficient of variation) for amoxicillin and 152.6% (64.3% coefficient of variation) for clavulanic acid between formulations. This pilot investigation supports the need for further bioequivalence studies regarding these formulations before commenting on product interchangeability.