Application of Caco-2 cell line in herb-drug interaction studies: current approaches and challenges.

Application of Caco-2 cell line in herb-drug interaction studies: current approaches and challenges.
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CACO-2细胞系在草本药物相互作用研究中的应用:当前的方法和挑战。

DOI:
10.18433/j30k63
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发表时间:
2014
期刊:
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
影响因子:
--
通讯作者:
Rosenkranz B
Rosenkranz B
中科院分区:
其他
文献类型:
--
作者:
Awortwe C;Fasinu PS;Rosenkranz B

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Caco-2模型在临床前研究中用于预测药物可能的胃肠道渗透性,因为它表达与人小肠具有相同特征的细胞色素P450酶、转运蛋白、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细胞系通过预测其溶解度,生物利用度和药物-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不可重现的数据。这些局限性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。本文综述了其中一些警告,并列举了合理的当前和未来的方法,以减少与Caco-2细胞系的调查,重点是其在草药相互作用的应用相关的异常。
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.
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