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Advances in the Prediction of Gastrointestinal Absorption: Quantitative Structure-Activity Relationship (QSAR) modelling of PAMPA Permeability

Diukendjieva, A, Tsakovska, I, Alov, P, Pencheva, T, Pajeva, I, Worth, A, Madden, J and Cronin, MTD (2018) Advances in the Prediction of Gastrointestinal Absorption: Quantitative Structure-Activity Relationship (QSAR) modelling of PAMPA Permeability. Computational Toxicology, 10. pp. 51-59. ISSN 2468-1113

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Abstract

Gastrointestinal absorption (GI absorption) is a key absorption, distribution, metabolism, and excretion (ADME) property when the biological effects of substances are evaluated. The Parallel Artificial Membrane Permeability Assay (PAMPA) has emerged as a primary screen for determining passive transcellular permeability, the dominant GI absorption mechanism for many drugs, thus helping with the prioritisation of the most promising lead compounds for pharmacokinetic studies. Recently the PAMPA assay has attracted increasing interest from various other industrial sectors, including cosmetics, where such non-animal models may provide a crucial source of information for in vitro - in vivo extrapolation. This method is also a reliable source of experimental data for Quantitative Structure-Activity Relationship (QSAR) modelling of GI absorption. In this investigation, published QSAR models for PAMPA were reviewed with the aim to summarise and assess critically the current state of the art. The review indicates a relatively small number of QSARs compared to some endpoints, but much consistency within the models. PAMPA permeability increases with hydrophobicity and decreases with the surface area occupied by hydrogen bond acceptor/donor atoms. The models can be applied to screening for bioactive compounds with the potential to pass the gastrointestinal barrier as well as to design new structures with increased PAMPA permeability, thus with better expectations towards improved in vivo GI absorption.

Item Type: Article
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 21 Dec 2018 09:43
Last Modified: 01 Apr 2019 12:24
URI: http://researchonline.ljmu.ac.uk/id/eprint/9862

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