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Human Intestinal Absorption (human + intestinal_absorption)
Selected AbstractsSimulation modelling of human intestinal absorption using Caco-2 permeability and kinetic solubility data for early drug discoveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Simon Thomas Abstract Measurement of permeation across a monolayer of the human adenocarcinoma cell line, Caco-2, is a popular surrogate for a compound's permeation across the human intestinal epithelium. Taken alone, however, Caco-2 permeability has certain limitations in the prediction of the extent of absorption of an orally-administered compound, because it does not take into account confounding factors such as solubility and dissolution in the gastrointestinal (GI) tract fluids. A simulation model is described that uses Caco-2 permeability measured in the apical to basolateral direction plus kinetic solubility in buffered solution (both measured at pH 7.4) to predict human intestinal absorption. The model features novel treatment of time-varying fluid volume in the GI tract, as a consequence of secretions into, and absorption of fluid from, the upper part of the GI tract. The model has been trained and cross-validated with data for 120 combinations of compound and dose. It has superior predictive power to recently published simulation and quantitative structure property relationship models, and is suitable for high-throughput screening during lead identification and lead optimisation in drug discovery. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4557,4574, 2008 [source] Quantitative structure/property relationship analysis of Caco-2 permeability using a genetic algorithm-based partial least squares methodJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2002Fumiyoshi Yamashita Abstract Caco-2 cell monolayers are widely used systems for predicting human intestinal absorption. This study was carried out to develop a quantitative structure,property relationship (QSPR) model of Caco-2 permeability using a novel genetic algorithm-based partial least squares (GA-PLS) method. The Caco-2 permeability data for 73 compounds were taken from the literature. Molconn-Z descriptors of these compounds were calculated as molecular descriptors, and the optimal subset of the descriptors was explored by GA-PLS analysis. A fitness function considering both goodness-of-fit to the training data and predictability of the testing data was adopted throughout the genetic algorithm-driven optimization procedure. The final PLS model consisting of 24 descriptors gave a correlation coefficient (r) of 0.886 for the entire dataset and a predictive correlation coefficient (rpred) of 0.825 that was evaluated by a leave-some-out cross-validation procedure. Thus, the GA-PLS analysis proved to be a reasonable QSPR modeling approach for predicting Caco-2 permeability. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2230,2239, 2002 [source] Retention data from reverse-phase high-performance thin-layer chromatography in characterization of some bis-salicylic acid derivativesBIOMEDICAL CHROMATOGRAPHY, Issue 8 2009-Sekuli, Tatjana Djakovi Abstract The chromatographic behaviour of salicylic acid derivatives was investigated using reversed-phase high performance thin-layer chromatography (RP HPTLC) with methanol,water and dioxane,water binary mixtures as mobile phase in order to establish relationships between chromatographic data and selected physico-chemical parameters that are related to ADME (absorption, distribution, metabolism and elimination). Some of the investigated compounds were screened for antioxidant activity. Examination of chromatographic behaviour revealed a linear correlation between RM values and the volume fraction of mobile phase modifier. Obtained RM0 values were correlated with lipophilicity, solubility, human intestinal absorption, plasma-protein binding, and blood,brain barrier data. The comparison among chromatographic data obtained by two mobile phase was performed with a statistical technique, principle component analysis. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||