Transporters in Drug Development: Discovery, Optimization, Clinical Study and Regulation (AAPS Advances in the Pharmaceutical Sciences Series Book 7)

__Transporters in Drug Development__ examines how membrane transporters can be dealt with in academic–industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of __in vitro__ characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters’ impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating __in vitro__ observed interaction of transporters into __in vivo__ relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process. Transporters in Drug Development examines how membrane transporters can be dealt with in academic-industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver, and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters' impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process. Yuichi Sugiyama is head of Sugiyama Laborator at RIKEN Innovation Center, RIKEN Research Cluster for Innovation in Yokohama, Japan, and previously professor in the Department of Molecular Pharmacokinetics at the University of Tokyo from 1991 through to his retirement from the University in 2012. He is coauthor of more than 580 publications in international journals as well as 270 book chapters and review articles. His work is internationally recognized by prestigious awards, including AAPS Distinguished Pharmaceutical Scientist Award (2003), FIP Hoest Madsen Gold Medal (2009), "Medal with Purple Ribbon" given by the government in 2010, and the B. Brodie Award from ASPET (2012). Professor Sugiyama has been ranked as the top-cited scientist in the field of Pharmacology & Toxicology (1997-2007). He served as the chairman of the Board of Pharmaceutical Sciences in FIP and was also the president of both the International Society for the Study of Xenobiotics (ISSX) and Japanese Society for Xenobiotic Metabolism and Disposition (JSSX). Bente Steffansen is associate professor in transporters in ADME at the Faculty of Health and Medical Sciences, University of Copenhagen. She graduated with MSc (pharm) in 1989 from the Royal Danish School of Pharmacy and obtained her PhD in 1994 under the Danish Research Academy within the field of prodrug design aimed for improved drug delivery. Dr. Steffansen has published more than 60 research articles, edited a book, and serves as the program director for pharmaceutical education at the University of Copenhagen. She is a member of the Chemical Committee under the National Pharmacopeia Board and a member of the European BioSim network of excellence Transporters in Drug Development is a corner stone in a high profile book series on advances in pharmaceutical sciences initiated by AAPS, Springer and Professor Daan Crommelin as series Editor. Transporters in Drug Development: Discovery, Optimization, Clinical Study and Regulation list chapters written by leading researchers in the transporter field from academia, pharmaceutical industry and medicines agencies. The book encompasses examples and advises on how membrane transporters can be dealt with in academic industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. Methods and examples of in vitro characterization of single transporters in intestine, liver and kidney are described as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are discussed as well as the perspectives of applying targeted proteomics and mechanistic modelling in this process Front Matter....Pages i-xiii Membrane Transporters in ADME....Pages 1-22 In Vitro Kinetic Characterization of Transporter-Mediated Permeability....Pages 23-35 In Vitro Characterization of Interactions with Drug Transporting Proteins....Pages 37-65 In Vivo Characterization of Interactions on Transporters....Pages 67-97 Applications of Targeted Proteomics in ADME for IVIVE....Pages 99-119 Prediction of Hepatic Transporter-Mediated Drug–Drug Interaction from In Vitro Data....Pages 121-153 Accounting for Transporters in Renal Clearance: Towards a Mechanistic Kidney Model (Mech KiM)....Pages 155-177 Analysis of Intestinal Transporters....Pages 179-199 Analysis of Hepatic Transport Proteins....Pages 201-233 Analysis of Renal Transporters....Pages 235-256 The Role of Transporters in Drug Development: Regulatory Science Perspectives from the FDA....Pages 257-283 Industrial Evaluation of Drug Transporters in ADME....Pages 285-307 Erratum....Pages E1-E1 Back Matter....Pages 309-317 The seventh volume of Advances in Pharmaceutical Sciences heralds a welcome continuation of this well-respected series. Acknowledged experts provide comprehensive statements of current research and development in selected fields of pharmaceutical technology. This book will be of great value to those working in academia and the pharmaceutical industry.