Prediction of Caco-2 pH-Dependent Permeability based on High-Quality in vitro Training Set
نویسنده
چکیده
[1] Ho, N.F.H., Raub, T.J., Burton, P.S., Barsuhn, C.L., Adson, A., Audus, K.L., Borchardt, R., 2000. Quantitative approaches to delineate passive transport mechanisms in cell culture monolayers. In: Amidon, G.L., Lee, P.I., Topp, E.M. (Eds.). Transport Processes in Pharmaceutical Systems. Marcel Dekker: New York, N.Y., pp. 219-316. [2] Avdeef, A., 2005. The Rise of PAMPA. Expert Opinion Drug Metab. Tox., 1, 325-342. [3] Bermejo, M., Avdeef, A., Ruiz, A., Nalda, R., Ruell, J.A., Tsinman, O., González, I., Fernández, C., Sánchez, G., Garrigues, T.M., Merino, V., 2004. PAMPA a drug absorption in vitro model. 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones. Eur. J. Pharm. Sci., 21, 429-441. [4] Youdim, K.A., Avdeef, A., Abbott, N.J., 2003. In vitro trans-monolayer permeability calculations: often forgotten assumptions. Drug Disc. Today, 8, 997-1003. [5] Avdeef, A., Artursson, P., Neuhoff, S., Lazarova, L., Gråsjö, J., Tavelin, S., 2005. Caco-2 Permeability of Weakly Basic Drugs Predicted with the Double-Sink PAMPA pK a flux Method. Eur. J. Pharm. Sci., 24, 333-349. [6] Abraham, M.H. The factors that influence permeation across the blood-brain barrier. Eur. J. Med. Chem. 2004, 39, 235-240. [7] Lanevskij, K.; Japertas, P.; Didziapetris, R.; Petrauskas, A. Ionization-specific prediction of blood-brain barrier permeability. J. Pharm. Sci. 2008, in press. DOI.10.1002/jps. [8] Neuhoff, S., Ungell, A.-L., Zamora, I., Artursson, P., 2005. pH-Dependent passive and active transport of acidic drugs across Caco-2 cell monolayers. Eur. J. Pharm. Sci., 25, 211-220. REFERENCES CONCLUSION
منابع مشابه
Comparison of in vitro models for the prediction of compound absorption across the human intestinal mucosa.
Several in vitro assays have been developed to evaluate the gastrointestinal absorption of compounds. Our aim was to compare 3 of these methods: 1) the bio-mimetic artificial membrane permeability assay (BAMPA) method, which offers a high-throughput, noncellular approach to the measurement of passive transport; 2) the traditional Caco-2 cell assay, the use of which as a high-throughput tool is ...
متن کاملPredicting Caco-2 permeability using support vector machine and chemistry development kit.
PURPOSE To predict Caco-2 permeability is a valuable target for pharmaceutical research. Most of the Caco-2 prediction models are based on commercial or special software which limited their practical value. This study represents the relationship between Caco-2 permeability and molecular descriptors totally based on open source software. METHODS The Caco-2 prediction model was constructed base...
متن کاملPrediction of the in vitro permeability determined in Caco-2 cells by using artificial neural networks.
Caco-2 cells are currently the most used in vitro tool for prediction of the potential oral absorption of new drugs. The existence of computational models based on this data may potentiate the early selection process of new drugs, but the current models are based on a limited number of cases or on a reduced molecular space. We present an artificial neural network based only on calculated molecu...
متن کاملADME Evaluation in Drug Discovery. 5. Correlation of Caco-2 Permeation with Simple Molecular Properties
The correlations between Caco-2 permeability (logPapp) and molecular properties have been investigated. A training set of 77 structurally diverse organic molecules was used to construct significant QSAR models for Caco-2 cell permeation. Cellular permeation was found to depend primarily upon experimental distribution coefficient (logD) at pH = 7.4, high charged polar surface area (HCPSA), and r...
متن کاملPermeation of Insulin, Calcitonin and Exenatide across Caco-2 Monolayers: Measurement Using a Rapid, 3-Day System
OBJECTIVES Caco-2 monolayers are one of the most widely used in vitro models for prediction of intestinal permeability of therapeutic molecules. However, the conventional Caco-2 monolayer model has several drawbacks including labor-intensive culture process, unphysiological growth conditions, lack of reproducibility and limited throughput. Here, we report on the use of 3-day Caco-2 monolayers f...
متن کامل