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目的用有限采样法(LSS)估算口服阿莫西林的生物等效性。方法 20名健康志愿者口服阿莫西林参比药物和受试药物500 mg后采集若干时间点血浆样品,用高效液相色谱法测定阿莫西林血药浓度,用经典方法计算药代动力学参数,评价生物等效性。另以参比药物血药浓度数据作为建模数据,用LSS法估算药代动力学参数Cmax、AUC0-t,选择最佳模型进行生物等效性评价。内外部验证均用Jackknife法。结果以2个和3个血药浓度数据点预测的药代动力学参数回归模型的线性关系较好。内部和外部验证表明:以血药浓度数据2点组合C1,C3和3点组合C1,C2,C4估算AUC0-t的准确性最好(预测误差<1%,绝对误差<10%);又以2点组合C1,C1.5和3点组合C1.5,C2,C6估算Cmax的准确性最好(预测误差<2%,绝对误差<10%);并以3点组合C1.5,C2,C6同时估算AUC0-t和Cmax的准确性较好。与经典法评价结果一致。结论用LSS法估算口服阿莫西林药代动力学参数评价生物等效性是可行的,为有限采样法评价生物等效性提供新的思路和计算方法。
Objective To estimate the bioequivalence of oral amoxicillin by finite sampling method (LSS). Methods A total of 20 healthy volunteers received 500 mg of amoxicillin as reference drug and test drug. Plasma samples were collected at several time points. Amoxicillin concentration was determined by HPLC. Pharmacokinetic parameters were calculated by classical method , To evaluate bioequivalence. Another reference drug plasma concentration data as modeling data, LSS method to estimate the pharmacokinetic parameters Cmax, AUC0-t, select the best model for bioequivalence evaluation. Internal and external validation using Jackknife method. Results The linearity of the pharmacokinetic regression model predicted by two and three plasma concentration data points was good. The internal and external validation showed that the accuracy of AUC0-t was best estimated by combining C1, C3 and 3 points C1, C2 and C4 with two points of plasma concentration data (prediction error <1% and absolute error <10%); The accuracy of Cmax was best estimated by combining C1.5, C2 and C6 with two combinations of C1, C1.5 and 3 (prediction error <2%, absolute error <10%); and the combination of C1.5, C2, C6 estimate AUC0-t and Cmax accuracy is better. Consistent with the results of the classic method. Conclusion It is feasible to estimate the bioequivalence of oral amoxicillin pharmacokinetic parameters by LSS method, and provide new ideas and calculation methods for evaluating the bioequivalence of finite sampling method.