LSS法估算中国健康志愿者口服阿莫西林的生物等效性  

Bioequivalence assessment of amoxicillin by limited sampling strategy in Chinese healthy volunteers

作　　者：陈丽芳[1] 焦建杰[2] 张才丽[2] 娄建石[2] 

机构地区：[1]天津市海河医院药剂科,天津300350 [2]天津医科大学基础医学院药理教研室,天津300070

出　　处：《中国临床药理学杂志》2012年第10期761-764,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：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 develop limited sampling strategy （LSS） for estimating bioequivalence of amoxicillin. Methods Twenty male healthy subjects were enrolled in this bioequivalence study. All subjects were di- vided into two groups randomly and administered orally reference and test formulation of 500 mg amoxicillin. The blood concentrations of amoxicil- lin were determined by the validated HPLC method. A multiple linear re- gression analysis was developed for estimating C and AUC0-t using the amoxicillin concentration of the reference formulation to develop LSS models. The LSS models were internally validated by the Jackknife meth- od. The models were also externally validated by bioequivalence assess- ment of the test amoxicillin formulation based on LSS derived C and AUC0-s,values, The results were compared with those obtained using tra- ditional method. Results The results indicate：several models for these parameters estimation met the predefined criteria. Validation tests indica- ted that most informative sampling points C1 , C3 and C1 , C2, C4 provided accurate estimations of the parameters AUC0_,. （ prediction error 〈 1%, absolute percentage 〈 10% ） ,And C1 , C1.5 and C1.5, C2, C6 provided ac- curate estimations of the parameters Cmax （ prediction error 〈 2%, abso- lute percentage 〈 9%）. The combination of C1.5, C2, C6 might bechosen as sampling hours for predicting AUC0_, and C according to requirement. It is according with classical assess- ment. Conclusion The bioequivalence assessment results showed that LSS models provided correct assessment of bio- equivalence between two amoxicillin preparations. The method is accurant and can be considered desirable for amoxicil- lin bioequivalence study.

关 键 词：有限采样法 阿莫西林 生物等效性 经典法 药代动力学 

分 类 号：R978.11[医药卫生—药品] R969.1[医药卫生—药学]