基于PBPK模型的在体单向肠灌流技术对苷元成分的适用性分析评价  

Applicability analysis and evaluation of aglycones in single-pass intestinal perfusion technique based on PBPK model

作　　者：刘洋[1] 张鑫[1] 石秀佳 温雅心 杨丽[1] 董玲[1] LIU Yang;ZHANG Xin;SHI Xiu-jia;WEN Ya-xin;YANG Li;DONG Ling(Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学

出　　处：《中国中药杂志》2019年第17期3645-3652,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81473362)

摘　　要：在体单向肠灌流技术(single-pass intestinal perfusion,SPIP)是生物药剂学分类系统(biopharmaceutics classification system,BCS)研究化合物渗透性的常用载体。随着BCS在中药领域的应用与深入,采用SPIP模型研究中药成分的肠吸收也愈来愈普遍。该研究基于SPIP模型在某些中药渗透性研究的局限性问题上,推测苷元可能比苷更适合采用SPIP模型研究肠吸收问题,并对其在苷元成分的适用性方面进行了分析和评价。以槲皮素、大豆苷元、芒柄花素、染料木素和甘草次酸为研究对象,通过SPIP的定量研究评估这几种苷元成分的肠道通透性并做人体有效渗透系数(Peff)和吸收分数(Fa)的预测。结合多种渗透性研究方法的文献对比分析及基于生理的药代动力学(physiologically based pharmacokinetic models,PBPK)模型对苷元成分的人体吸收预测,以进一步说明SPIP模型是研究中药苷元渗透性及预测人体吸收的良好工具,为单向肠灌流技术和BCS在中药成分的肠吸收研究方面提供数据基础及理论参考。Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.

关 键 词：生物药剂学分类系统 PBPK模型 SPIP 苷元 渗透性 

分 类 号：R28[医药卫生—中药学]