Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, Cape Town, South Africa.
J Pharm Pharm Sci. 2014;17(1):1-19. doi: 10.18433/j30k63.
The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions.
Caco-2 模型被用于临床前研究中，以预测药物的胃肠道渗透性，因为它表达了与人类小肠相同特征的细胞色素 P450 酶、转运体、微绒毛和肠细胞。FDA 建议将该模型作为生物药剂学分类系统（BCS）的组成部分。大多数专门的实验室使用 Caco-2 细胞系通过预测其在肠道腔中的溶解度、生物利用度以及药物-药物或草药-药物相互作用的可能性来筛选新的化学实体。然而，Caco-2 细胞固有特性的挑战和实验室间方案的变化导致产生了不可重现的数据。这些限制影响了从临床前研究到涉及药物-药物和草药-药物相互作用的临床研究的数据外推。这篇综述讨论了其中的一些注意事项，并列举了目前和未来可能减少与 Caco-2 细胞系研究相关的异常的方法，重点是其在草药-药物相互作用中的应用。
