The Bioequivalence Studies Of Amoxicillin And Clavulanic Acid In Beagles

This experiment carried out bioequivalence study comparing amoxicillin and clavulanate potassium tablets producted by Shibide Biotechnology Co.LTD from Lai’an county, Anhui Province and Zoetis company from Americian.In this study, a UPLC-MS/MS method was developed to detect the amoxicilin and clavulanic acid in dog plasma. The calibration curve for amoxicilin and clavulanic acid were linear in the range of 10～1000 ng/m L（P>0.997）. Concentration of three quality control samples（0.1,1and10μg/m L） of intra-day and inter-day precisions, and the low density of less than 20%, the Concentration and high Concentration less than 20%. The limit of detection（LOD） and the limit of quantification（LOQ） of method were respectively5ng/m L and 10ng/m L. The method was so simple, rapid, effective and that it is suitable to detect the amoxicilin and clavulanic acid in the dogs plasma.In bioequivalence tests, a crossover design trial was used with randomized assignment to alternative two oral formulations. We select 20 healthy adult beagle dogs, weighing9.5^-10.5kg, according to amoxicillin at a dose of 10 mg·kg^-1, administered at a dose of clavulanic acid is 2.5 mg·kg^-1 to the dog orally, to measured at different times after drug plasma concentrations of amoxicillin and clavulanic acid.The reference of amoxicillin in dogs in vivo pharmacokinetic parameters are as follows: the Tmax was 1.93±0.71 h, Cmax was 6867.01±2295.08 ng·m L^-1, AUC0-t was21512.29±10156.23 h·ng·m L^-1, AUC0-∞ was 21918.59±10251.61 h·ng·m L^-1. The reference of clavulanic acid in dogs in vivo pharmacokinetic parameters are as follows: the Tmax was1.38±0.72 h, Cmax was 1048.78±466.65 ng·m L^-1, AUC0-t was 1929.86±1559.48 h·ng·m L^-1and AUC0-∞ was 2113.04±1623.82 h·ng·m L^-1.The test of amoxicillin in dogs in vivo pharmacokinetic parameters are as follows: the Tmax was 1.88±0.82 h, Cmax was 6586.50±1049.17 ng·m L^-1, AUC0-t was19648.51±4733.61 h·ng·m L^-1, AUC0-∞ was 20028.40±4835.56 h·ng·m L^-1. The test of clavulanic acid in dogs in vivo pharmacokinetic parameters are as follows: the Tmax was1.36±0.56 h, Cmax was 1411.28±751.34 ng·m L^-1, AUC0-t was 2173.46±1134.62 h·ng·m L^-1and AUC0-∞ was 2379.62±1173.42 h·ng·m L^-1.The test results showed that there was no significant differencen（P>0.05） the major pharmacokinetic parameters（AUC0-t, AUC0-∞, Tmax and Cmax） between the test tablet and its reference tablet.After bioequivalence statistical analysis, a single administration of two formulations of amoxicillin and clavulanic acid AUC0-t, AUC0-∞, Tmax and Cmax of 90% confidence intervals were within the range of 80 to 125%.In conclusion, the test tablet have good bioequivalent compared with reference tablet.