Drug Transporters. Molecular Characterization and Role in Drug Disposition

This book provides a comprehensive and up-to-date coverage of the relationship between drug metabolism enzymes and transporters on drug toxicity, along with methods to investigate their role on adverse drug reactions. Unites both the metabolism and transporter components of drug toxicity – two aspects not normally connected and the latter often neglected Familiarizes readers with the mechanism and species differences in drug metabolizing enzymes and transporters Discusses promising approaches to accurately predict human drug toxicity via the incorporation of human drug metabolism in toxicity evaluation

DRUG TRANSPORTERS [b]Drug transporter fundamentals and relevant principles and techniques, featuring new and expanded chapters Drug Transporters: Molecular Characterization and Role in Drug Disposition provides in-depth analysis of the conceptual evolution and technical development for studying drug transporters. Contributions by an international panel of leading researchers address advances in transporters as drug targets, transporters in pharmacotherapy, the impact of transporters on drug efficacy and safety, the development of sophisticated model systems and sensitive assay methods, and more. Divided into two parts, the book first provides a thorough overview of relevant drug transporters before detailing the principles of drug transport and associated techniques. The updated and expanded third edition includes new chapters on in vitro-in vivo scale-up of drug transport activities, the ontogeny of drug transporters, the application of physiologically-based pharmacokinetic and pharmacodynamic modeling, and the use of transporters as therapeutic targets for diseases. Reflects the current state of the field and offers perspectives on future directions Covers basic knowledge, clinical outcomes, and emerging discoveries in transporter science Provides up-to-date information on drug transporter families, mechanisms, and clinical implications Includes extensive references and numerous figures and tables throughout Understandable for novices while offering sufficient depth for more experienced researchers, Drug Transporters: Molecular Characterization and Role in Drug Disposition, Third Edition is an excellent textbook for pharmacological or physiological science courses in drug/membrane transport, and an invaluable reference for academic or industrial scientists working in the transporter field and related areas of drug metabolism, pharmacokinetics, and pharmacodynamics.

Covers powerful new tools for drug development Molecular pathology offers tools and techniques that can greatly enhance the drug discovery and development process, helping to make the promises of personalized medicine a reality. Molecular Pathology in Drug Discovery and Development provides an unmatched guide to this cutting-edge discipline and its applications to pharmaceutical science. With contributions from leading lights in drug discovery, drug development, and molecular pathology balanced by a consistent editorial approach, this reference offers both an overview of molecular pathology and a close look at the methods as they are applied to the process of drug discovery and development. Presented as steps in the drug development process, the coverage includes the use of molecular pathology to: Identify and validate new drug candidates Enhance transcriptional profiling to better find and validate biomarkers Assess toxicology Employ toxicogenomics to identify genes relevant to the safety of compounds Identify correct doses for different drugs Identify patients for treatment Develop molecular therapies Further the new techniques of Immunohistochemistry and Immunofluorescence With many tests and treatments already working today, drug research and development using molecular pathology has shown itself an extremely fruitful area. Molecular Pathology in Drug Discovery and Development gives practitioners an up-to-date resource on this highly active discipline and its role in furthering pharmaceutical research.

This reference handbook is the first to provide a comprehensive overview, systematically characterizing all known transporters involved in drug elimination and resistance. Combining recent knowledge on all known classes of drug carriers, from microbes to man, it begins with a look at human and mammalian transporters. This is followed by microbial, fungal and parasitic transporters with special attention given to transport across those physiological barriers relevant for drug uptake, distribution and excretion. As a result, this key resource lays the foundations for understanding and investigating the molecular mechanisms for multidrug resistance in cancer cells, microbial resistance to antibiotics and pharmacokinetics in general. For anyone working with antibiotics and cancer chemotherapeutics, as well as being of prime interest to biochemists and biophysicists.

As opposed to other books on the topic, this volume is unique in also covering emerging transporter targets. Following a general introduction to the importance of targeting transporter proteins with drugs, the book systematically presents individual transporter classes and explains their pharmacology and physiology. The text covers all transporter families with known or suspected importance as drug targets, including neurotransmitter transporters, ABC transporters, glucose transporters and organic ion transporters. The final part discusses recent advances in structural studies of transport proteins, assay methods for transport activity, and the systems biology of transporters and their regulation. With its focus on drug development issues, this authoritative overview is required reading for researchers in industry and academia targeting transport proteins for the treatment of disease.

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.

The essentials of drug metabolism vital to developing new therapeutic entities Information on the metabolism and disposition of candidate drugs is a critical part of all aspects of the drug discovery and development process. Drug metabolism, as practiced in the pharmaceutical industry today, is a complex, multidisciplinary field that requires knowledge of sophisticated analytical technologies and expertise in mechanistic and kinetic enzymology, organic reaction mechanism, pharmacokinetic analysis, animal physiology, basic chemical toxicology, preclinical pharmacology, and molecular biology. With chapters contributed by experts in their specific areas, this reference covers: * Basic concepts of drug metabolism * The role of drug metabolism in the pharmaceutical industry * Analytical techniques in drug metabolism * Common experimental approaches and protocols Drug Metabolism in Drug Design and Development emphasizes practical considerations such as the data needed, the experiments and analytical methods typically employed, and the interpretation and application of data. Chapters highlight facts, common protocols, detailed experimental designs, applications, and limitations of techniques. This is a comprehensive, hands-on reference for drug metabolism researchers as well as other professionals involved in pre-clinical drug discovery and development.

This first systematic overview for more than a decade is tailor-made for the medicinal chemist. All the chapters are written by experienced drug developers and include practical examples from real drug candidates. Following an introduction to global drug properties and their impact on drug research, screening and combinatorial chemistry libraries, this handbook demonstrates the best and fastest way to estimate those properties most relevant for the efficiency and pharmacokinetic performance of a drug molecule: lipophilicity,solubility, electronic properties and conformation.