中药复方化学成分众多，各成分的化学结构、理化性质、作用靶点和药代（PK）行为各不相同，且多种成分间还普遍存在药代和药效相互作用。目前中药复方的PK研究多局限于某些成分的孤立研究，既缺乏对多组分PK相互作用及作用机制的系统研究，又缺乏表征复方整体PK行为的有效方法。前期研究发现，在临床常用剂量下大黄黄连泻心汤主要活性物质（黄连生物碱和大黄蒽醌）有明显PK间相互作用，该PK相互作用与代谢酶和转运体有关。因此我们以大黄黄连泻心汤为研究对象，先采用酶、细胞、器官与动物模型，研究基于转运体和代谢酶介导的多组分PK间相互作用及作用机制；然后运用PopPK固定效应模型构建基于多组分PK相互作用效应的整体PK模型；并仿真和验证该模型。建立符合中药特色的基于复方多组分PK间相互作用效应的整体PK研究方法。应用该PK模型阐释和预测复方中多种组分间PK相互作用关系和复方的整体PK行为，为指导临床合理用药提供理论依据。

Traditional Chinese medicine (TCM) which are composed of a large number of chemicals, its chemical structure, physical and chemical properties, targets and pharmacokinetic (PK) behavior of each compound are varied. Besides, widespread drug pharmacokinetic and pharmacodynamic interactions are existence among various components. Currently, the PK study of TCM was based on isolated certain ingredients, neither systematic research based on the interaction between PK and multi-component mechanism of action, nor an effective method was applied to characterize the behavior of the compound as an integral PK. Based on previous studies, we found that the clinical dose of Xiexintang, which main active substances (isoquinoline alkaloids and anthraquinone) possess significant PK interaction, which was induced by the related metabolic enzymes and transporters. Therefore, the TCM Xiexintang was selected for this research, the enzyme, cells, organs and animal model are selected to study the drug interaction and its mediated mechanisms between multi-component by PK based on transporters and metabolic enzymes; then the fixed effects model was applied to establish the integrative PK model based on PopPK model of those multi-component and its interaction effect; and then the overall PK model was by means of simulation and verification. The overall PK model was characterization of TCM to reflect the multi-component interaction effect of the PK and methodology for the overall PK model study, which could be applied to illustrate and estimate the multi-component PK interaction relationship and the overall PK property of TCM, this study could be provided a theoretical basis for clinical therapy in application of TCM.

中药复方化学成分众多，各成分的化学结构、理化性质、作用靶点和药代（PK）行为各不相同，且多种成分间还普遍存在药代和药效相互作用。目前中药复方研究，既缺乏对多组分PK相互作用及作用机制的系统研究，又缺乏表征复方整体PK行为的有效方法。我们研究研究发现，在临床常用剂量下泻心汤主要活性物质（黄连生物碱，大黄蒽醌和黄芩黄酮）有明显PK间相互作用，该PK相互作用与代谢酶和转运体有关。因此我们以泻心汤为研究对象，先采用酶、细胞、器官与动物模型，研究基于转运体和代谢酶介导的多组分PK间相互作用及作用机制；然后运用PopPK固定效应模型构建基于多组分PK相互作用效应的整体PK模型；并仿真和验证该模型。建立符合中药特色的基于复方多组分PK间相互作用效应的整体PK研究方法。应用该PK模型阐释和预测复方中多种组分间PK相互作用关系和复方的整体PK行为，在黄连生物碱的作用下，大黄蒽醌类成分的重要药代动力学参数明显改变，AUC增加一倍，且与代谢酶抑制作用密切相关。该模型能够说明药药相互作用而改变的整体PK参数，为指导临床合理用药提供理论依据。