摘要
本研究以药动学参数为指标,评价有限采样法估算二甲双胍药动学参数的可行性,为二甲双胍的生物等效性评价及临床监测提供实验依据。以20名健康志愿者为研究对象,口服盐酸二甲双胍1 000 mg后采集若干时间点血浆样品,采用高效液相色谱法测定各采样时间点二甲双胍的血药浓度,以LSS建立回归数学模型,用Jacknife法验证回归模型的准确性。结果表明,单个血药浓度-时间点预测药动学参数,回归模型,线性关系较差;部分2点和3点预测药动学参数,回归模型,线性关系较好(r2>0.9,P<0.05),其中以C2,C6预测AUC0?24 h和C1.5,C2预测Cmax的回归模型和线性关系最佳,且准确性好。因此,有限采样法估算口服盐酸二甲双胍制剂药动学参数是可行的。
The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy（LSS）,which will provide scientific data for bioequivalence and clinical application.A single dose of metformin was administrated to 20 healthy volunteers.The concentration of metformin in whole blood was determined by validated high performance liquid chroma-tography（HPLC） method.Multi-linear regression analysis was performed to establish a model to estimate AUC0？24 h and Cmax of metformin by LSS method.The LSS models were validated by the Jackknife method.The result indicated： the linearity relationship between AUC0？24 h or Cmax and single concentration point was poor.Several models for metformin AUC0？24 h or Cmax estimation were better（r2 0.9,P 0.05）.Validation tests indicated that most informative sampling points（C2,C6 for AUC0？24 h,C1.5,C2 for Cmax） provided accurate estimations of these parameters.So,a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.
出处
《药学学报》
CAS
CSCD
北大核心
2010年第12期1533-1536,共4页
Acta Pharmaceutica Sinica
基金
国家重点基础研究发展计划(973计划)资助项目(2004CB518902)
关键词
盐酸二甲双胍
有限采样法
药动学参数
metformin hydrochloride
limited sampling strategy
pharmacokinetic parameter
