HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: In vitro in vivo correlation with permeability data from rats and humans
HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: In vitro in vivo correlation with permeability data from rats and humans
复制标题
DOI：
10.1021/js960110x
复制
发表时间：
1996-10-01
影响因子：
3.8
通讯作者：
Amidon, GL
中科院分区：
文献类型：
--
作者：
Walter, E;Janich, S;Amidon, GL
肠上皮的多种分泌和吸收功能是由吸收细胞和产生粘液的杯状细胞作为主要细胞类型的混合群体执行的。为了接近体外模型的主要特征，开发了吸收性 Caco-2 细胞和分泌粘液的 HT29-MTX 细胞的共培养系统，并测试了一系列不同药物的渗透性。可以实现可变的杯状细胞频率，保留药物转运的显着屏障并保持两种细胞类型的差异化特征。与体内数据相比，细胞培养模型中主动转运药物的吸收率被低估。然而，与人体吸收分数有良好的相关性，将被动转运的药物范围分为两组 P-eff 大于或等于 10 x 10(-6) cm/s 的吸收良好的化合物和 P-eff = 0.1-1 x 10(-6) cm/s 吸收率为 40-70% 的药物。对于低吸收性药物，建议渗透性 P-eff < 0.1 x 10(-6) cm/s。
The diverse secretory and absorptive functions of the intestinal epithelium are conducted by a mixed population of absorptive cells and mucus-producing goblet cells as the major cell types. In order to approach the main characteristics in an in vitro model, a coculture system of absorptive Caco-2 cells and mucus-secreting HT29-MTX cells was developed and the permeability of a range of different drugs was tested. Variable goblet cell frequency can be achieved, preserving a significant barrier to drug transport and maintaining the differentiated features of both cell types. Absorption rates for actively transported drugs are rather underestimated in the cell culture model when compared to in vivo data. However, a good correlation with fraction absorbed in humans was attained separating the range of passively transported drugs into two groups of well-absorbable compounds with P-eff greater than or equal to 10 x 10(-6) cm/s and drugs that are absorbed 40-70% with P-eff = 0.1-1 x 10(-6) cm/s. A permeability of P-eff < 0.1 x 10(-6) cm/s is suggested for low absorbable drugs.