Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption

Newby, Danielle, Freitas, Alex A and Ghafourian, Taravat (2015) Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption. European Journal of Medicinal Chemistry, 90. pp. 751-765. ISSN 0223-5234

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Oral absorption of compounds depends on many physiological, physiochemical and formulation factors. Two important properties that govern oral absorption are in vitro permeability and solubility, which are commonly used as indicators of human intestinal absorption. Despite this, the nature and exact characteristics of the relationship between these parameters are not well understood. In this study a large dataset of human intestinal absorption was collated along with in vitro permeability, aqueous solubility, melting point, and maximum dose for the same compounds. The dataset allowed a permeability threshold to be established objectively to predict high or low intestinal absorption. Using this permeability threshold, classification decision trees incorporating a solubility-related parameter such as experimental or predicted solubility, or the melting point based absorption potential (MPbAP), along with structural molecular descriptors were developed and validated to predict oral absorption class. The decision trees were able to determine the individual roles of permeability and solubility in oral absorption process. Poorly permeable compounds with high solubility show low intestinal absorption, whereas poorly water soluble compounds with high or low permeability may have high intestinal absorption provided that they have certain molecular characteristics such as a small polar surface or specific topology. © 2014 Published by Elsevier Masson SAS.

Item Type: Article
Keywords: cytochrome P450 3A4; ketoconazole; mebendazole; ziprasidone, Article; decision tree; drug absorption; drug solubility; human; hydrogen bond; in vitro study; intestine absorption; intestine mucosa permeability; melting point; absorption; animal; CACO 2 cell line; dog; MDCK cell line; oral drug administration; permeability; solubility, Absorption, Physiological; Administration, Oral; Animals; Caco-2 Cells; Decision Trees; Dogs; Humans; Madin Darby Canine Kidney Cells; Permeability; Solubility
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 01 Dec 2017 07:21
Last Modified: 09 Mar 2021 15:15

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