Investigation of Factors Affecting the Performance of in silico Volume Distribution QSAR Models for Human, Rat, Mouse, Dog & Monkey

Molecular Informatics
Saw SimeonMatthew Paul Gleeson

Abstract

Volume of distribution (Vdss ) is a measure of how effectively a drug molecule is distributed throughout the body. Along with the clearance, it determines the half-life and therefore the drug dosing interval. A number of different pre-clinical approaches are available to predict the Vdss in human including quantitative structure activity relationship (QSAR) models. Vdss QSAR models have been reported for human and rat, but not important pre-clinical species including dog, mouse and monkey. In this study, we have generated Vdss QSAR model on the human and commonly used pre-clinical species, each of which differs in terms of size, chemical diversity and data quality. We discuss the model performance by species, assess the effect the domain of applicability and the relative merits of building chemical series-specific models. In addition, we compare the intrinsic variability of the experimental logVdss data (∼1.2 fold error) to in-vivo interspecies differences (∼2 fold error) and in silico based models (∼3 fold error). This prompted us to explore whether one species could be used to predict another, particularly where little data for that species is available. i. e. does the expansion in domain of applicability prove beneficial ove...Continue Reading

References

Jan 5, 2002·Journal of Molecular Graphics & Modelling·L H Hall, L B Kier
Sep 23, 2003·Journal of Pharmaceutical Sciences·Olivier LuttringerThierry Lavé
Mar 18, 2004·The Journal of Pharmacy and Pharmacology·Taravat GhafourianMark T D Cronin
Mar 17, 2006·Journal of Medicinal Chemistry·M Paul GleesonAndrew M Davis
May 16, 2006·International Journal of Pharmaceutics·Taravat GhafourianAli Nokhodchi
Jul 19, 2006·Drug Discovery Today·Igor V TetkoGennadiy I Poda
Sep 5, 2006·ChemMedChem·Ulf Norinder, Christel A S Bergström
Sep 11, 2007·Journal of Nutrition Education and Behavior·Mary S Willis, Janet S Buck
Feb 1, 2008·Journal of Medicinal Chemistry·M Paul Gleeson
Mar 11, 2008·Journal of Molecular Graphics & Modelling·Shane Weaver, M Paul Gleeson
Jul 4, 2008·Bioinformatics·Yiqun CaoThomas Girke
Jul 17, 2009·Journal of Medicinal Chemistry·Giuliano BerelliniFranco Lombardo
May 5, 2010·Drug Discovery Today·Sean EkinsJames T Metz
Jun 18, 2010·Drug Discovery Today·Andrew T Chadwick, Matthew D Segall
Jun 25, 2010·Journal of Chemical Information and Modeling·Denis FourchesAlexander Tropsha
Mar 2, 2011·Nature Reviews. Drug Discovery·M Paul GleesonJohn Overington
Mar 23, 2011·Journal of Computational Chemistry·Chun Wei Yap
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Feb 10, 2012·Current Pharmaceutical Design·M Paul GleesonRobert C Glen
May 31, 2012·Journal of Medicinal Chemistry·Christian KramerAnna Vulpetti
Jun 1, 2012·Expert Opinion on Drug Discovery·Dino MontanariTino Rossi
Aug 2, 2012·Expert Opinion on Drug Metabolism & Toxicology·Matthew Paul Gleeson, Dino Montanari
Jan 16, 2013·Molecular Pharmaceutics·Andrew M Davis, David J Wood
Mar 5, 2013·Journal of Chemical Information and Modeling·Vijay K Gombar, Stephen D Hall
Apr 25, 2013·PloS One·Tuomo KalliokoskiPeter Gedeck
Apr 26, 2013·Journal of Computer-aided Molecular Design·Richard CoxStephen D Pickett
Jun 13, 2013·Journal of Medicinal Chemistry·Matthew F BrownRichard P Zaniewski
Oct 29, 2013·Journal of Chemical Information and Modeling·Pekka TiikkainenLutz Franke
Dec 20, 2013·Journal of Medicinal Chemistry·Artem CherkasovAlexander Tropsha

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