Chen Li-fang, Jiao Jian-jie, Zhang Cai-li, Lou Jian-shi, Liu Chang-xiao
Tianjin Haihe Hospital, Tianjin 300350, China.
Yao Xue Xue Bao. 2010 Dec;45(12):1533-6.
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 chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 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.
本研究旨在采用有限采样策略（LSS）估算20名中国健康志愿者体内盐酸二甲双胍的药代动力学参数，为生物等效性和临床应用提供科学数据。给20名健康志愿者单次服用二甲双胍。采用经过验证的高效液相色谱（HPLC）法测定全血中二甲双胍的浓度。进行多线性回归分析以建立模型，通过LSS法估算二甲双胍的AUC(0 - 24 h)和Cmax。采用留一法对LSS模型进行验证。结果表明：AUC(0 - 24 h)或Cmax与单一浓度点之间的线性关系较差。几种估算二甲双胍AUC(0 - 24 h)或Cmax的模型较好（r2 > 0.9，P < 0.05）。验证试验表明，大多数信息丰富的采样点（AUC(0 - 24 h)的C2、C6，Cmax的C1.5、C2）能准确估算这些参数。因此，采用LSS法估算二甲双胍药代动力学参数的多线性回归模型是可行的。
