Drug Transporters

William A. Murphy,Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Sibylle Neuhoff,Simcyp Division, Certara UK Ltd., Sheffield, UK

Anne T. Nies,Dr. Margarete Fischer‐Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany; Cluster of Excellence iFIT (EXC2180) “Image‐Guided and Functionally Instructed Tumor Therapies,” University of Tuebingen, Tuebingen, Germany

Sanjay K. Nigam,Departments of Pediatrics and Medicine, University of California, San Diego, CA, USA

Stefan Oswald,Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany

Antonio López Quiñones,Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA

Tianjing Ren,Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

Robert W. Robey,Laboratory of Cell Biology, Multidrug Resistance Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Patrick T. Ronaldson,Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA

Amin Rostami‐Hodjegan,Simcyp Division, Certara UK Ltd., Sheffield, UK; Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, UK

Andaleeb Sajid,Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Vishal Sangha,Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

Noora Sjöstedt,Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

Tore B. Stage,Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark

Yuichi Sugiyama,Laboratory of Quantitative Systems Pharmacokinetics/Pharmacodynamics, Faculty of Pharmaceutical Sciences, Josai International University, Chiyoda‐ku, Tokyo, Japan

Peter W. Swaan,Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA

Douglas H. Sweet,School of Pharmacy, Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA

Rommel G. Tirona,Departments of Physiology & Pharmacology and Medicine, The University of Western Ontario, London, Ontario, Canada

Jashvant D. Unadkat,Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA

Manthena V. S. Varma,ADME Sciences, Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research & Development, Pfizer Inc, Groton, CT, USA

Joanne Wang,Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA

Erica I. Williams,Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA

Victoria Woo,Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA

Guofeng You,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

Jinghui Zhang,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

Qing Zhang,Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, USA

The contributions by the leaders in the field of drug transport to the 1st and the 2nd editions of Drug Transporters have helped to secure a special role for this book in the education of students, fellows, and industrial practitioners in the pharmaceutical and biomedical sciences. The 2nd edition was published 8 years ago. Since then, there has been significant advances in the field including in‐depth understanding of membrane transporters in pediatric pharmacotherapy, new insights into the impact of these transporters on drug efficacy/safety, development of more sophisticated model systems and sensitive assay methods for studying drug transport in vitro and in vivo, and knowledge of transporters as drug targets for diseases. Therefore, it has become clear that a 3rd edition that serves to capture current advances in the field is both timely and necessary.

The new (3rd) edition will preserve the same basic format as that of the previous two editions: the first half of the book provides an overview of the relevant drug transporters useful for both beginning and experienced scientists and researchers. The second half of the book presents the principles of drug transport and associated techniques in sufficient detail to enable nonspecialist readers to understand them. Such readers include graduate students in the pharmacological or physiological sciences and academic or industrial scientists in related fields of study. There are 25 chapters in the 3rd edition as compared with 23 chapters in the 2nd edition. This represents an update of most of the chapters, significant expansion of others, removal of chapters for which content has been incorporated into other chapters, and addition of four new chapters. New chapters include in vitro – in vivo scale‐up of drug transport activities, application of physiologically based pharmacokinetic and pharmacodynamic modeling to delineating the role of various factors in drug disposition and toxicity, the ontogeny of drug transporters, and transporters as therapeutic targets for diseases. As a result, the new edition not only reflects where the field is today but where it will be for the foreseeable future. Like its predecessor, it is anticipated that the new edition will continue to be used as a textbook in graduate courses in Drug/Membrane Transport and as a desk reference for researchers working in the transporter field, as well as in the areas of drug metabolism and pharmacokinetics/pharmacodynamics in the pharmaceutical industry.

We would like to express our deepest gratitude and respect to our colleagues who contributed chapters in their area of expertise. The book was written and edited during an especially difficult and challenging time of global pandemic, with many of our colleagues being affected both professionally and personally. We are indebted to all of our contributors. We acknowledge the many professionals at John Wiley & Sons, Inc. who worked with us to ensure the best book possible. On a personal note, we thank our families for their love and support.

Guofeng You and Marilyn E. Morris

Guofeng You 1and Marilyn E. Morris 2

1 Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

2 Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

Since the discovery of transporter‐mediated drug transport, and the subsequent cloning and functional characterization of the individual transporter, our understanding of the roles of drug transporters play in human physiology, diseases, and drug therapy has exploded. Information about any of the many diverse aspects of drug transporters is scattered very widely, from journals of microbiology to those of pharmacology and genetics. Furthermore, many different, often conflicting, explanations given for these transporters need to be reconciled and rationalized. With such a need, comes this book Drug Transporters . This book, now in its 3rd edition, compiles and synthesizes the diverse body of knowledge on currently known drug transporters. This chapter provides an overview on the basic concepts/properties of drug transporters to serve as a foundation, allowing readers the opportunity to become familiar with those notions prior to reading the following chapters in the entire book.