www.clinical.proteomics-journal.com Page 1 Proteomics - Clinical Applications Received: 30-Sep-2014; Revised: 16-Jan-2015; Accepted: 05-Feb-2015 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/prca.201400147. This article is protected by copyright. All rights reserved. The Role of Quantitative ADME Proteomics to Support Construction of Physiologically-Based Pharmacokinetic Models for Use in Small Molecule Drug Development Aki T. Heikkinen 1,a , Floriane Lignet 2 , Paul Cutler 2 , Neil Parrott 2,* 1 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland 2 Pharmaceutical Sciences, Pharmaceutical Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland a Current affiliation: Admescope Ltd, Oulu, Finland * CORRESPONDING AUTHOR Neil Parrott Pharmaceutical Sciences Roche Pharmaceutical Research and Early Development Roche Innovation Center Basel Grenzacherstrasse 124, B70/R130 CH-4070 Basel Switzerland Tel: +41 61 68 80813 E-mail: neil_john.parrott@roche.com List of abbreviations ABC – ATP-binding cassette; ADME – absorption, distribution, metabolism, and excretion; BCRP – breast cancer resistance protein; CYP – cytochrome P450; IVIVE – in vitro to in vivo extrapolation; MDR1 – multidrug resistance protein 1, also known as P-glycoprotein (P-gp); mRNA – messenger RNA; MRP2 – multidrug resistance associated protein 2; OATP – organic anion transporting polypeptide; PD – pharmacodynamics; PK – pharmacokinetics; PBPK – physiologically-based pharmacokinetics; SLC – solute carrier; UGT – uridiŶe 5-diphospho glucuronosyltransferase;