冠心Ⅱ号方中芍药苷的群体药代动力学

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CL1、V1、CL2、V2、Ka0及Kal的群体拟合值分别为0.509L/h,0.104 L,0.113L/h,0.123L,0.135 h-1及0.0135 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Ka1、Ka0和V1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.%To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin.Plasma concentration of Paeonifiorin 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,VI,CL2,V2,Ka0,and Kal,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 eovariate of Kal,Ka0,and V1.It is concluded that the pharnaacokinetic behaviors of paeonifiorin in rats can alter with different dose formulations.