Caco-2细胞模型在口服药物吸收研究中的应用

目的对Caco 2细胞模型在口服药物肠吸收研究中的应用作一综述。方法在引用了自1974~2004年的32篇文献的基础上,通过介绍并比较体外Caco 2模型和体内药物吸收转运的不同途径,讨论Caco 2单层细胞模型在预测不同类药物体内吸收中的作用。结果Caco 2细胞模型可以预测不同转运途径的药物体内吸收,尤其适用于被动转运药物,这一细胞模型在药物吸收机制、处方组成透膜性和黏膜毒性、药物吸收过程中的相互作用、药物的化学结构和体内转运关系、药物吸收限速因素、药物代谢稳定性及pH对药物吸收的影响等研究中均有较广泛的应用。结论Caco2细胞模型用于预测各种途径的药物吸收,在细胞水平上提供了大量与吸收相关的信息,是口服药物高通量筛选的良好工具。

Important application of Caco-2 cell monolayers in the study of the intestinal oral absorption

Objective To review the important applications of Caco2 cell monolayers in the study of the intestinal absorption of oral drug.Methods Based on 32 papers published from 1974 to 2004,the different routes of drug transport in Caco2 cell monolayers are compared with those seen in vivo and the prediction of drug absorption in vivo from transport experiments in cell monolayers is discussed for different classes of drug.Results Caco2 cell monolayers model could predict the absorption of drugs transported by different routes,especially for the passive transport drugs,this cell model was applied extensively in the study of the mechanism of absorption,permeability and toxity to mucous membrane of drug formulation component,interactions between drugs in the process of absorption,relationship between the chemical structures and transport in vivo,restricted step of absorption,metabolism of drugs and the effect of pH on the absorption.Conclusions(Caco2) cell monolayers model can predict the absorption of drugs transported by different routes and provide a large amount of information related to the drug absorption.It can be used as effective tool for oral drug high-throughput screening.