Pharmacogenomics of Human Drug Transporters: Clinical Impacts

Sets the foundation for safer, more effective drug therapies

With this book as their guide, readers will discover how to apply our current understanding of the pharmacogenomics of drug transporters to advance their own drug discovery and development efforts. In particular, the book explains how new findings in the field now enable researchers to more accurately predict drug interactions and adverse drug reactions. Moreover, it sets the foundation for the development of drug therapies that are tailored to an individual patient's genetics.

Pharmacogenomics of Human Drug Transporters serves as a comprehensive guide to how transporters regulate the absorption, distribution, and elimination of drugs in the body as well as how an individual's genome affects those processes. The book's eighteen chapters have been authored by a team of leading pioneers in the field. Based on their own laboratory and clinical experience as well as a thorough review of the literature, these authors explore all facets of drug transporter pharmacogenomics, including:

Individual drug transporters and transporter families and their clinical significance Principles of altered drug transport in drug–drug interactions, pharmacotherapy, and personalized medicine Emerging new technologies for rapid detection of genetic polymorphisms Clinical aspects of genetic polymorphisms in major drug transporter genes Future research directions of drug transporter pharmacogenomics and the prospect of individualized medicine

Pharmacogenomics of Human Drug Transporters opens the door to new drug discovery and development breakthroughs leading to safer and more effective customized drug therapies.The book is recommended for pharmaceutical scientists, biochemists, pharmacologists, clinicians, and genetics and genomics researchers.

PREFACE vii

CONTRIBUTORS ix

CHAPTER 1 INTRODUCTION TO PHARMACOGENOMICS OF DRUG TRANSPORTERS 1
Marianne K. DeGorter and Richard B. Kim

CHAPTER 2 ADME PHARMACOGENOMICS IN DRUG DEVELOPMENT 13
Liangfu Chen and Joseph W. Polli

CHAPTER 3 REGULATORY PERSPECTIVE ON PHARMACOGENOMICS OF DRUG-METABOLIZING ENZYMES AND TRANSPORTERS 39
Lei Zhang, Gilbert J. Burckart, Lawrence J. Lesko and Shiew-Mei Huang

CHAPTER 4 THE PHARMACOGENOMICS OF MEMBRANE TRANSPORTERS PROJECT 73
Sook Wah Yee, Deanna L. Kroetz and Kathleen M. Giacomini

CHAPTER 5 EMERGING NEW TECHNOLOGY OF SNP TYPING 109
Toshihisa Ishikawa and Yoshihide Hayashizaki

CHAPTER 6 OATP1A2, OAT1, AND OAT3 125
Rommel G. Tirona

CHAPTER 7 OATP1B1, OATP1B3, AND OATP2B1 141
J¨org K¨onig and Martin F. Fromm

CHAPTER 8 OCT (SLC22A) AND OCTN FAMILY 171
Sophie L. Stocker, Arian Emami Riedmaier, Matthias Schwab and Kathleen M. Giacomini

CHAPTER 9 MATE (SLC47) FAMILY 209
Atsushi Yonezawa and Ken-ichi Inui

CHAPTER 10 PEPT (SLC15A) FAMILY 223
Tomoko Sugiura, Saki Umeda, Akira Tsuji and Yukio Kato

CHAPTER 11 NUCLEOSIDE TRANSPORTERS (SLC28 AND SLC29) FAMILY 243
M´ýriam Molina-Arcas and Marc¸al Pastor-Anglada

CHAPTER 12 P-GLYCOPROTEIN (MDR1/ABCB1) 271
Ingolf Cascorbi

CHAPTER 13 BSEP (ABCB11) 295
Bruno Stieger and Gerd A. Kullak-Ublick

CHAPTER 14 BCRP (ABCG2) 311
Agnes Basseville, Susan E. Bates, William D. Figg and Alex Sparreboom

CHAPTER 15 MRP2 (ABCC2) AND MRP3 (ABCC3) 345
Anne T. Nies

CHAPTER 16 MRP4 (ABCC4) 365
Satish B. Cheepala, Mugdha Sukthankar and John D. Schuetz

CHAPTER 17 MRP8 (ABCC11) 387
Yu Toyoda and Toshihisa Ishikawa

CHAPTER 18 FUTURE PERSPECTIVES 401
Toshihisa Ishikawa and Joseph Ware

INDEX 417