Ingels F, Deferme S, Delbar N, Oth M, Augustijns P
Biopharmaceutics & Drug Delivery, Lilly Development Centre, Mont-Saint-Guibert, Belgium.
J Pharm Belg. 2002 Nov-Dec;57(6):153-8.
The Caco-2 cell culture model is widely used during drug development and lead optimization as a predictive tool for the oral absorption of drugs. In order to improve the reliability and quality of the results of Caco-2 experiments and to ensure that the system being used is functionally and enzymatically representative for the intestinal mucosa, it is important to perform a validation of the implemented Caco-2 system. In this paper, we summarize evaluation techniques to guarantee the in-house validity of the model. Theophyllin and sodium fluorescein are used as model compounds to evaluate passive transcellular and passive paracellular transport, respectively. Phenylalanine serves as a substrate to demonstrate active carrier mechanisms. Aminopeptidase and dipeptidyl peptidase are two brush border enzymes present in an active form in the Caco-2 culture model. The presence of an active efflux carrier mechanism is demonstrated with cyclosporin A as a substrate.
Caco-2细胞培养模型在药物研发和先导化合物优化过程中被广泛用作药物口服吸收的预测工具。为提高Caco-2实验结果的可靠性和质量，并确保所使用的系统在功能和酶活性方面能够代表肠黏膜，对所实施的Caco-2系统进行验证非常重要。在本文中，我们总结了评估技术以确保该模型在内部的有效性。分别使用茶碱和荧光素钠作为模型化合物来评估被动跨细胞转运和被动细胞旁转运。苯丙氨酸用作底物以证明主动载体机制。氨肽酶和二肽基肽酶是Caco-2培养模型中以活性形式存在的两种刷状缘酶。以环孢素A为底物证明了活性外排载体机制的存在。
