药物通透性在新药发现和开发阶段的评估策略  

Assessment strategies for drug permeability during drug discovery and development

作　　者：李文倩 韩静静 张贤 徐润泽 杨劲[1] LI Wen-qian;HAN Jing-jing;ZHANG Xian;XU Run-ze;YANG Jin(Center of Drug Metabolism and Pharmacokinetics,School of Pharmaceutical Sciences,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院药物代谢研究中心,江苏南京210009

出　　处：《药学学报》2021年第5期1279-1285,共7页Acta Pharmaceutica Sinica

摘　　要：通透性是影响口服药物生物利用度的一个关键性因素,因此,新药研发的早期阶段,准确及高效地评估药物通透性至关重要。工业界通常将平行人工膜渗透技术(parallel artificial membrane permeability assay, PAMPA)和Caco-2细胞模型作为早期评估方法,目前,尤斯灌流大鼠模型也被广泛的应用。本篇综述首先总结了人体内单次灌注技术(in vivo single-pass perfusion technique, Loc-I-Gut)的数据—金标准,然后着重介绍了三种体外方法的基本原理、实验操作、效率、与人体内有效通透性(effective permeability coefficient, Peff)数据和人体吸收分数(fraction absorbed, Fa)的相关性,以期为在新药发现和开发的不同阶段使用正确的通透性方法提供建议。Permeability is a key factor in the bioavailability of oral drugs.Therefore,in the early stage of drug discovery,accurate and efficient evaluation of drug permeability is essential.The parallel artificial membrane permeability assay(PAMPA)with Caco-2 cells model was used by the industry as early evaluation methods.At present,the Ussing chamber rat model is also widely used.This review summarizes the human data for the in vivo single-pass perfusion technique(Loc-I-Gut)–the gold standard,and then focuses on the basic principles,experimental operation,and efficiency of the three in vitro methods,with correlation to the effective permeability coefficient(Peff)and fractional absorbed(Fa)in man.We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.

关 键 词：口服药物 通透性 平行人工膜渗透技术 CACO-2 尤斯灌流 有效通透性 吸收分数 

分 类 号：R917[医药卫生—药物分析学]