基于含药肠吸收-肝孵育液药理法的麻黄-杏仁药对体外PK-PD模型研究初探

PK-PD结合模型研究是中药现代化的重要领域，但其经典方法难以准确阐释中药复杂的体内过程，讫需探讨更适合的研究思路和方法。体外研究是药理学的重要组成，而含药肠吸收-肝孵育液药理法是中药体外PK和PD研究的桥梁和纽带，故我们提出了“基于该药理法的中药体外PK-PD结合模型研究”的新思路与方法，有望逐步解析中药与机体间的相互作用及规律。本研究以麻黄-杏仁药对为对象，药对疗喘主要有效成分群为指标，经离体肠吸收和肝细胞代谢动力学研究，NCA分析获取整合PK模型；以反映收缩和分泌功能的主效应群为指标，经体外组织、细胞水平药效学研究，AIC原则获取整合PD模型；将上述数据经模拟得出PK-PD模型，预测C'/C'e、T、E间的相互关系及特征。通过本项目的示范性研究，进一步完善“含药肝孵育液药理法”方法体系，为中药PK-PD结合模型研究提供新思路和方法，促进麻黄-杏仁药对配伍科学内涵的现代阐释。

PK-PD combined model research is an important field of modernization of TCM, but its classical methods are difficult to accurately explain the complex in vivo processes of it, so more suitable research ideas and methods need to be developed. In vitro experiments is an important part of pharmacological research, and play an increasingly important role in the study of TCM PK-PD. The drug-containing intestinal absorption-hepatic incubation solution pharmacology is the bridge and bond of TCM in vitro PK and PD research. Therefore, the study of the in vitro PK-PD binding model based on this method is expected to gradually analyze the complex interactions and laws between TCM and the body. Therefore, we have proposed a new idea and method of "Research on in vitro PK-PD binding model of TCM based on Drug-containing Hepatic Incubation Solution Method ". This study is based on the pharmacological method, and ephedra-almond couplet is used as the object. The main active ingredient groups of anti-asthma that have been previously identified are used as indicators, an integrated PK model is obtained by NCA analysis after the intestinal absorption kinetics and hepatocyte metabolic kinetics study. The main effects reflecting contractile and secretory functions were used as indicators and AIC as the main discriminant principle, explore an integrated PD model that affects the bronchial ring and smooth muscle cell spasm models. The above data will be integrated to obtain a PK-PD binding model, and preliminary predictions of the interrelationship between the two, or three of C, T, and E. Through the demonstration research of this project, the method system of "Drug-containing Hepatic Incubation Solution Method" will be further improved, which will provide ideas and methods for the study of TCM PK-PD combination model, and promote the modern interpretation of the scientific connotation of compatibility of ephedra-almond couplet.