Walter E, Janich S, Roessler B J, Hilfinger J M, Amidon G L
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
J Pharm Sci. 1996 Oct;85(10):1070-6. doi: 10.1021/js960110x.
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 Peff > or = 10 x 10(-6) cm/s and drugs that are absorbed 40-70% with Peff = 0.1-1 x 10(-5) cm/s. A permeability of Peff < 0.1 x 10(-5) cm/s is suggested for low absorbable drugs.
肠道上皮的多种分泌和吸收功能主要由吸收细胞和分泌黏液的杯状细胞这两种混合细胞群体来执行。为了在体外模型中探究主要特征，开发了吸收性Caco-2细胞和分泌黏液的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，同时保持对药物转运的显著屏障，并维持两种细胞类型的分化特征。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，将被动转运药物范围分为两组，即有效渗透率（Peff）≥10×10⁻⁶ cm/s的易吸收化合物组和Peff = 0.1 - 1×10⁻⁵ cm/s时吸收率为40 - 70%的药物组，该模型与人体吸收分数具有良好的相关性。对于低吸收性药物，建议其Peff < 0.1×10⁻⁵ cm/s。
