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冠心II号方中芍药苷的群体药代动力学

陈文倩, 胡渝慧, 张彦青, 张关敏, 李良, 杨维宁, 卢炜*   

  1. 1.北京大学药学院 药剂学系, 北京 100083;
    2.北京大学 天然药物及仿生国家重点实验室, 北京 100083
  • 收稿日期:2007-07-24 修回日期:2008-01-10 出版日期:2008-03-15 发布日期:2008-03-15
  • 通讯作者: 卢炜*

Population pharmacokinetics of paeoniflorin in guanxin II prescription

Wen-Qian Chen, Yu-Hui Hu, Yan-Qing Zhang, Guan-Min Zhang, Liang Li, Wei-Ning Yang, Wei Lu*   

  1. 1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China;
    2. The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China
  • Received:2007-07-24 Revised:2008-01-10 Online:2008-03-15 Published:2008-03-15
  • Contact: Wei Lu*

摘要:

本研究旨在分析冠心II号方中组分的变化对芍药苷药动学性质的影响。将大鼠随机分组后分别静脉注射芍药苷提取物(PPE)、灌胃给予PPE及三种不同组成的水煎液, HPLC法测定给药后不同时间血浆中芍药苷浓度, 并用非线性混合效应模型(NONMEM)法对全部数据进行药动学模型拟合。吸收相中带有一级降解速率的二室口服吸收模型可以用于描述芍药苷的体内药动学特征, 药动学参数CL1V1CL2V2Ka0 Ka1的群体拟合值分别为0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135 h-10.0135 h-1, 模型对个体间差异进行了估计, 并以给药剂型 (DF) 作为固定效应对参数Ka1Ka0V1进行了校正。群体药动学方法可以用于分析冠心 II号中组方变化对芍药苷体内吸收和分布产生的影响。

关键词: 芍药苷, 芍药苷, 芍药苷, 群体药代动力学, 群体药代动力学, 群体药代动力学, 中药, 中药, 中药, 冠心II号, 冠心II号, 冠心II号, 中药复方, 中药复方, 中药复方

Abstract:

To evaluate the effect of components in Guanxin II prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract (PPE) and oral administration of PPE and three types of decoctions in Guanxin II prescription, respectively, were determined by HPLC analyses. NONMEM (nonlinear mixed-effect modeling) method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Ka1, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation (DF) was identified as a significant covariate of Ka1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.

Key words: Paeoniflorin, Paeoniflorin, Population pharmacokinetics, Population pharmacokinetics, Traditional Chinese Medicine, Traditional Chinese Medicine, Guanxin II, Guanxin II, Compound formulae, Compound formulae

中图分类号: 

Supporting: Foundation item: National Natural Science Foundation (Grant No. 30472165).
*Corresponding author. Tel./fax: 86-10-82801717