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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)](P<0.05)。阿莫西林和克拉维酸分别在剂量1 000~4 000 mg、62.5~250mg剂量范围内呈线性药代动力学特征。以最小抑菌浓度(MIC)为2.0μg·ml~(-1)计,单次口服低、中、高剂量的阿莫西林/克拉维酸钾缓释片后,12 h内血药浓度大于MIC的持续时间(T>MIC)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%。
OBJECTIVE: To optimize the clinical dosage regimen of amoxicillin / clavulanate sustained-release tablets according to PK / PD parameters. Methods: Thirty healthy subjects were randomly divided into three groups. Oxymorin / clavulanate sustained-release tablets were orally administered fasting, pre-meal and postprandial, respectively, and the optimal dosage was determined by comparing their pharmacokinetic characteristics. Three groups of subjects were orally low, medium and high doses of amoxicillin / clavulanate three doses of sustained-release tablets, comparing different doses PK / PD parameters to determine the dose and dosing interval . Results: Compared with the pre-meal group [(41.7 ± 1.92) μg · h · ml -1] in the Amoxicillin AUC fasting group [(32.2 ± 15.0) μg · h · ml -1] and postprandial (42.6 ± 17.7 μg · h · ml -1), while the AUC of clavulanic acid in the postprandial group was (1.89 ± 0.54) μg · h · ml -1 (2.55 ± 0.76) μg · h · ml -1 in fasting group and 2.58 ± 0.76 μg · h · ml -1 in meal group (P <0.05). Amoxicillin and clavulanic acid showed linear pharmacokinetic characteristics in the dose range of 1 000-4 000 mg and 62.5-250 mg respectively. With a minimum inhibitory concentration (MIC) of 2.0 μg · ml ~ (-1), after a single oral low, medium and high doses of amoxicillin / clavulanate sustained-release tablets, the plasma concentration within 12 h was greater than The duration of MIC (T> MIC) was 5.5, 7 and 10 h, respectively, with the percentages being 46%, 58% and 83% respectively. When the MIC was 4.0 μg · ml -1, the T> MICs were 4.5, 6 and 8 h in 12 h respectively, with the percentages being 38%, 50% and 67%, respectively. CONCLUSIONS: The best time to give amoxicillin / clavulanate sustained-release tablets is to take a standard meal of 2 to 2 times per day to achieve 40% to 50% at T> MIC.