Billat Pierre-André, Roger Emilie, Faure Sébastien, Lagarce Frédéric
MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, France.
MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, France; Pharmacy Department, Angers University Hospital, Angers, France.
Drug Discov Today. 2017 May;22(5):761-775. doi: 10.1016/j.drudis.2017.01.007. Epub 2017 Jan 20.
The small intestine is a complex organ with movements, flora, mucus and flows. Despite this, the most widely used absorption models consider the organ a cylindrical monoepithelial tube. This review presents the recent evolution of models to take into consideration the complex nature of gut physiology. The most commonly encountered issues are ethical (in vivo models) and differences in drug transport as a result of a modified expression of drug transporters or metabolic enzymes compared with human (in vitro and in vivo models). Finally, this review discusses the way forward to reach an ideal equilibrium between reproducibility, predictability and efficiency for predicting permeability. The features of an ideal model are listed as a guideline for future development.
小肠是一个具有蠕动、菌群、黏液和流体的复杂器官。尽管如此，最广泛使用的吸收模型将该器官视为圆柱形单上皮管。本综述介绍了模型的最新进展，以考虑肠道生理学的复杂性质。最常见的问题是伦理问题（体内模型）以及与人类相比，由于药物转运体或代谢酶表达改变导致的药物转运差异（体外和体内模型）。最后，本综述讨论了在预测通透性的可重复性、可预测性和效率之间达到理想平衡的前进方向。列出了理想模型的特征作为未来发展的指导方针。
