Abstract
This study aimed to evaluate the pharmacokinetic characteristics and bioequivalence of a test and a reference formulation of amoxicillin-clavulanate potassium tablets in dogs.Twenty-four healthy golden retrievers were randomly divided into two groups and subjected to a randomized,single-dose,two-period,two-treatment,two-sequence crossover design.Each dog was orally administered a single dose of 25 mg/(kg·bw)of either the test or reference formulation.Blood samples were collected via the cephalic vein at pre-dose(0 h)and at 0.083,0.25,0.5,0.75,1,1.25,1.5,1.75,2,2.5,3,4,6,8,and 12 h post-administration.The UPLC-MS/MS method was validated for linearity,specificity,limit of detection(LOD),limit of quantification(LOQ),accuracy,precision,matrix effect,and stability.Plasma concentrations of amoxicillin and clavulanate were determined using UPLC-MS/MS,and key pharmacokinetic parameters including maximum concentration(Cmax),time to maximum concentration(Tmax),and area under the curve(AUC0-t and AUC0-∞)were calculated using WinNonlin 8.1 to assess bioequivalence.The method showed excellent linearity within the ranges of 20-5 000 ng/mL for amoxicillin and 50-2 000 ng/mL for clavulanate(R2≥0.99),with good specificity.The LOD and LOQ for amoxicillin were 10 and 20 ng/mL,respectively,and for clavulanate were 20 and 50 ng/mL,respectively.Mean recoveries of amoxicillin and clavulanate were 89.88%-111.64%and 94.00%-114.48%,respectively,with good precision and matrix effects within acceptable ranges.Both drugs were stable in blank plasma.The concentration-time curves of the test and reference formulations were generally consistent.For amoxicillin,the Tmax values of the test and reference formulations were(2.34±0.74)and(2.13±0.59)h,respectively;the Cmax values were(8.88±2.43)and(9.00±2.25)µg/mL;the AUC₀₋ₜ values were(38.22±9.05)and(37.44±9.51)(µg/mL)·h;and the AUC0-∞ values were(39.23±9.17)and(38.07±9.69)(µg/mL)·h.For clavulanate,the Tmax values of the test and reference formulations were(1.31±0.36)and(1.27±0.28)h,respectively;the Cmax values were(2.36±0.78)and(2.71±1.37)µg/mL;the AUC0-t values were(5.47±1.30)and(5.19±2.00)(µg/mL)·h;and the AUC0-∞ values were(5.73±1.16)and(5.33±1.98)(µg/mL)·h.Bioequivalence analysis showed that the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were 98.20%,102.73%,and 103.81%for amoxicillin,and 90.44%,109.05%,and 111.67%for clavulanate,respectively.The 90%confidence intervals for all parameters were within the accepted range of 80.00%-125.00%,meeting the technical requirements for bioequivalence.These results indicate that the two formulations are bioequivalent and can be used interchangeably in clinical settings,providing a reliable reference for veterinary drug application.关键词
犬/阿莫西林/克拉维酸/生物等效性Key words
dog/amoxicillin/clavulanate/bioequivalence分类
农业科技
