Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.%目的:依据PK/PD参数优化阿莫西林/克拉维酸钾缓释片的临床给药方案.方法:30名健康受试者随机分为3组,分别于空腹、餐前和餐后口服阿莫西林/克拉维酸钾缓释片,通过比较其药动学特征确定最佳给药方式.3组受试者分别单次口服低、中、高3个剂量的阿莫西林/克拉维酸钾缓释片,比较不同给药剂量下的PK/PD参数,确定给药剂量和给药间隔.结果:阿莫西林的AUC空腹组[(32.2±15.0)μg·h·ml-1]较餐前组[(41.7±1.92)μg·h·ml-1]和餐后组[(42.6±17.7)μg·h·ml-1]有所降低,而克拉维酸的AUC则是餐后组[(1.89±0.54)μg·h·ml-1]明显低于空腹组[(2.55±0.76)μg·h·ml-1]和餐前组[(2.58±0.76)μg·h·ml-1](PMIC)分别为5.5,7,10 h,百分比分别为46%、58%和83%.以MIC为4.0μg·ml-1,则12 h内T>MIC分别为4.5,6,8 h,百分比分别为38%、50%和67%.结论:给予阿莫西林/克拉维酸钾缓释片的最佳时机是在标准餐前服用,每天给药2次,每次2片即可满足T>MIC时达到40%~50%.
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