阿莫西林克拉维酸钾不同配比制剂中克拉维酸的生物利用度研究

Study on bioavailability of clavulanic acid in amoxicillin-clavulanic acid preparations of different ratios

目的:对阿莫西林克拉维酸钾不同配比制剂中克拉维酸钾的生物利用度进行研究,为阿莫西林克拉维酸钾最优配比提供比较依据与评价标准。方法:通过建立克拉维酸的生理药动学(physiologically based pharmacokinetic,PBPK)模型,对不同配比阿莫西林克拉维酸钾制剂中克拉维酸的药动学过程进行模拟,计算对应生物利用度,并与β-内酰胺酶抑酶率、MIC90等药效相关参数进行关联研究。结果:在阿莫西林与克拉维酸钾1∶1~14∶1的范围内克拉维酸的生物利用度与抑酶率呈线性关系,对应R2=0. 969 7。结论:阿莫西林克拉维酸钾复方制剂中7∶1和8∶1制剂为疗效与药物经济学角度的最优配比产品。

Objective:To study the bioavailability of clavulanic acid in amoxicillin-clavulanic acid preparations of different ratios to provide evidence and assessment approach for the optimal combination ratio between amoxicillin and clavulanic potassium.Methods:The pharmacokinetics of clavulanic acid in amoxicillin clavulanate potassium was simulated by establishing a physiologically based pharmacokinetic(PBPK)model of clavulanic acid,and then the corresponding bioavailability was calculated and the correlation between bioavailability,β-lactamase-inhibitory rates and MIC90 was evaluated.Results:There was a linear relationship between the bioavailability of clavulanic acid and enzyme inhibition rate in the range of amoxicillin to clavulanic potassium combining ratio from 1∶1 to 14∶1,with R2=0.969 7.Conclusion:The combining ratios of 7∶1 and 8∶1 between amoxicillin and clavulanate potassium in the compound preparation are the best combination in terms of clinical efficacy and pharmacoeconomics.