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How LC-MS Proteomics Is Revolutionizing PBPK Modeling and Simulation

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Drug-metabolizing enzymes and drug transporters play an important role in hepatic drug metabolism and disposition and therefore have major implications on the fate of drugs in the human body. Recently, an increasing number of studies have reported proteomic expression data for pharmacologically relevant enzymes and transporters providing rich data that can be used for simulation and modeling. However, systematic analysis and understanding of the expression of these proteins in human tissue and commonly used in vitro systems is lacking.

New LC-MS techniques in quantitative proteomics are transforming the approach to quantitative pharmacology and in vitro-in vivo extrapolation (IVIVE) for physiologically-based pharmacokinetic (PBPK) models. In this webinar, Dr. Amin Rostami (Certara) and Dr. Brahim Achour (University of Manchester) discussed the scientific and economic implications of this approach on the IVIVE of enzyme and transporter-mediated drug pharmacokinetics using PBPK models.

講師紹介

Amin Rostami, Chief Scientific Officer, Certara. Dr. Rostami leads a team of scientists working on extrapolation of in vitro data on drug metabolism to predict in vivo pharmacokinetics and pharmacodynamics in virtual patient populations. He has authored/co-authored around 115 peer-reviewed full articles. Dr. Rostami has been the Scientific Secretary of PKUK (the UK discussion group on PK) since 1998, elected Scientific Secretary for the Drug Metabolism Committee of IUPHAR since 2010, and is an elected member of the EUFEPS Council. Currently he serves on the EUFEPS Committee on Industrial Research Relation, the HESI Emerging Issues Steering Committee (EISC), the ISSX Finance Committee and the Host Madsen Award Committee of FIP. He also serves on the editorial boards of Biopharmaceutics and Drug Disposition, Drug Metabolism & Pharmacokinetics, Current Drug Metabolism, Frontiers in Drug Metabolism and Transport and Frontiers in Toxicity Prediction and Xenobiotica. He has been an invited speaker at over 110 national and international meetings and he regularly leads hands-on workshops on model-based drug development. In November 2011, Amin was awarded a Japanese Society for the Study of Xenobiotics (JSSX) Fellowship for being ‘a distinguished contributor and acknowledged leader in the advancement of the study of xenobiotics’.

Dr. Rostami received his PharmD from Tabriz Medical Sciences University in 1987, and his PhD from the University of Sheffield in 1996. He was a Research Assistant to Professor Geoff Tucker before progressing to Lecturer (1997), Senior Lecturer (2002), Reader (2005) and Professor (2008) at Sheffield. He became Chair of Systems Pharmacology at the Centre for Applied Pharmacokinetic Research in the School of Pharmacy and Pharmaceutical Sciences at the University of Manchester, UK in 2009.

Brahim Achour, Research Associate, University of Manchester. Dr. Achour obtained a Master of Pharmacy (MPharm) degree from the Manchester Pharmacy School at the University of Manchester, UK, in 2007 (First Class). He then went on to complete a PhD program in the application of LC-MS to the characterization of drug-metabolizing enzymes in human liver at the Manchester Pharmacy School (2009-2013). In 2013, Dr. Achour started a brief post-doctoral project at the University of Manchester in the development of LC-MS assays to quantify transporters in the human liver and intestine, which was then extended to a second post-doctoral position in 2014 in the application of LC-MS methods to the quantification of drug-metabolizing enzymes and transporters in different in vitro and in vivo systems relevant to drug pharmacokinetics in the liver, intestine, kidney and brain.

Drug-metabolizing enzymes and drug transporters play an important role in hepatic drug metabolism and disposition and therefore have major implications on the fate of drugs in the human body. Recently, an increasing number of studies have reported proteomic expression data for pharmacologically relevant enzymes and transporters providing rich data that can be used for simulation and modelling. However, systematic analysis and understanding of the expression of these proteins in human tissue and commonly used in vitro systems is lacking.

New LC-MS techniques in quantitative proteomics are transforming the approach to quantitative pharmacology and in vitro-in vivo extrapolation (IVIVE) for physiologically-based pharmacokinetic (PBPK) models. In this webinar, Dr. Amin Rostami (Certara) and Dr. Brahim Achour (University of Manchester) discussed the scientific and economic implications of this approach on the IVIVE of enzyme and transporter-mediated drug pharmacokinetics using PBPK models.

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