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 (doi:10.1016/j.ejmech.2014.12.006)

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Abstract

Oral absorption 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.

Item Type:	Article
Additional Information:	[1] The 'Author's Accepted Manuscript' verson is attached with this GALA record. Please cite this article as: D. Newby, A.A. Freitas, T. Ghafourian, Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption, European Journal of Medicinal Chemistry (2015), doi: 10.1016/j.ejmech.2014.12.006. [2] Publisher's note (Elsevier): This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Uncontrolled Keywords:	intestinal absorption, permeability, solubility, decision trees, QSAR
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:	Publisher
Last Modified:	20 Oct 2016 14:00
URI:	http://gala.gre.ac.uk/id/eprint/12715

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