阿莫西林克拉维酸钾不同配比不同剂型的药代动力学研究

Pharmacokinetics of amoxicillin and clavulanate potassium at different proportions and dosage forms

目的通过探究不同配比、不同剂型阿莫西林克拉维酸钾在健康大鼠体内的药代动力学情况,对比生物利用度、半衰期、最大血药浓度等参数,为阿莫西林克拉维酸钾最优配比和剂型选择提供依据以及评价标准。方法利用LC-MS法测定大鼠分别灌胃阿莫西林克拉维酸钾颗粒(4∶1、7∶1)、阿莫西林克拉维酸钾分散片(4∶1、7∶1)和阿莫西林克拉维酸钾干混悬剂(4∶1、7∶1和14∶1)后24 h内阿莫西林血药浓度,用DAS 2.0计算药代动力学参数。结果阿莫西林克拉维酸钾配比相同时,干混悬剂和颗粒剂药代动力学参数相近,均优于分散片;剂型相同时,阿莫西林克拉维酸钾配比7∶1时的最大血药浓度和生物利用度优于4∶1。结论阿莫西林克拉维酸钾配比为7∶1时,剂型为干混悬剂和颗粒剂时,药代动力学参数表现更好。

Objective To determine the pharmacokinetics of amoxicillin and clavulanate potassium with different proportions and dosage forms in healthy rats by comparing the bioavailability,halflife and maximum blood concentration,to provide evidence and evaluation criteria for the optimal proportion and dosage form of amoxicillin and clavulanate potassium.Methods The plasma concentrations of amoxicillin in rats within 24 h after the intragastric administration of amoxicillin clavulanate potassium granules(4∶1;7∶1),amoxicillin and clavulanate potassium dispersible tablets(4∶1;7∶1),amoxicillin and clavulanate potassium dry suspension(4∶1;7∶1 and 14∶1)were detected by LC-MS.The pharmacokinetic parameters were calculated with DAS 2.0 software.Results At the same ratio of amoxicillin and clavulanate potassium,the pharmacokinetic parameters of dry suspension and granule were similar,and both had better than dispersive tablets.With the same dosage form,the maximum blood concentration and bioavailability of amoxicillin and clavulanate potassium ratio of 7∶1 was better than 4∶1.Conclusion The pharmacokinetic parameters are more favorable with amoxicillin to clavulanate potassium at 7∶1 in the form of dry suspension and granules.