Pharmacogenomics Of Human Drug Transporters

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Pharmacogenomics of Human Drug Transporters

Author : Toshihisa Ishikawa,Richard B. Kim,Jörg König
Publisher : Wiley
Page : 440 pages
File Size : 51,8 Mb
Release : 2013-04-15
Category : Medical
ISBN : 0470927941

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Pharmacogenomics of Human Drug Transporters by Toshihisa Ishikawa,Richard B. Kim,Jörg König Pdf

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.

Drug Transporters

Author : Glynis Nicholls,Kuresh Youdim
Publisher : Royal Society of Chemistry
Page : 239 pages
File Size : 54,7 Mb
Release : 2016-08-17
Category : Science
ISBN : 9781782628705

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Drug Transporters by Glynis Nicholls,Kuresh Youdim Pdf

Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. The first volume comprehensively reviewed current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics. In this second volume on Drug Transporters, emphasis is placed on emerging sciences and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.

Transporters and Drug-Metabolizing Enzymes in Drug Toxicity

Author : Albert P. Li
Publisher : John Wiley & Sons
Page : 530 pages
File Size : 43,6 Mb
Release : 2021-07-27
Category : Medical
ISBN : 9781119170846

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Transporters and Drug-Metabolizing Enzymes in Drug Toxicity by Albert P. Li Pdf

TRANSPORTERS AND DRUG-METABOLIZING ENZYMES IN DRUG TOXICITY Explore up-to-date coverage on the interaction between drug metabolism enzymes, transporters, and drug toxicity with this leading resources Transporters and Drug-Metabolizing Enzymes in Drug Toxicity delivers a comprehensive and updated review of the relationship between drug metabolism, transporters, and toxicity, providing insights into a major challenge in drug development – accurate assessment of human drug toxicity. Combining two disciplines frequently considered independently of one another, the book combines drug metabolism and toxicology with a focus on the role of biotransformation on drug toxicity and as a major factor for species and individual differences. Mechanism and species differences in drug metabolizing enzymes and transporters are discussed, as are the methods used to investigate the role of drug metabolizing enzymes and transporters in drug toxicity. Finally, the distinguished authors describe promising new experimental approaches to accurately assessing human drug toxicity via the consideration of human-specific drug metabolism in toxicity assays. In addition to topics as diverse as extended clearance models, experimental approaches for the estimation of DILI potential of drug candidates and roles of transporters in renal drug toxicity, readers will also enjoy the inclusion of such subjects as: A thorough overview of and introduction to drug metabolism and transporters and drug toxicity An exploration of drug metabolism enzymes and transporter activities as risk factors of marketed drugs associated with drug-induced fatalities A discussion of human-based in vitro experimental models for the evaluation of metabolism-dependent drug toxicity A treatment of mechanism-based experimental models for the evaluation of BSEP inhibition and DILI An examination of transporters and cochlea toxicity Perfect for scientists, students, and practitioners with interests in metabolism, toxicology, and drug development in the pharmaceutical industry, Transporters and Drug-Metabolizing Enzymes in Drug Toxicity will also earn a place in the libraries of medicinal chemists, pharmacologists, biochemists, toxicologists, and regulators in the pharmaceutical and health industries.

Membrane Transporters in Drug Discovery and Development

Author : Qing Yan
Publisher : Humana Press
Page : 357 pages
File Size : 55,8 Mb
Release : 2011-08-25
Category : Medical
ISBN : 1607617153

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Membrane Transporters in Drug Discovery and Development by Qing Yan Pdf

Studies of membrane transporters have had a great impact on our understanding of human diseases and the design of effective drugs. In Membrane Transporters in Drug Discovery and Development: Methods and Protocols, expert researchers provide practical methodologies of the ongoing research on membrane transporters, considering applications of transporter technologies in drug discovery and development. Chapters include new and useful fields and methodologies, including pharmacogenomics, nutrigenomics, systems biology, bioinformatics, nuclear magnetic resonance (NMR), imaging, and quantitative real-time-PCR. Transporter studies in drug discovery and development for various diseases are discussed, including neuropsychiatric disorders, cardiovascular diseases, ophthalmic diseases, cancer, and diabetes. Composed in the highly successful Methods in Molecular BiologyTM series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Wide-ranging and current, Membrane Transporters in Drug Discovery and Development: Methods and Protocols delivers a collection of practical protocols that can be used immediately in the lab, along with critical surveys of key topics by leading researchers in the field.

Hepatobiliary Transport: From Bench to Bedside

Author : S. Matern,J.L. Boyer,D. Keppler,P.J. Meier-Abt
Publisher : Springer Science & Business Media
Page : 196 pages
File Size : 40,8 Mb
Release : 2001-12-31
Category : Medical
ISBN : 0792387716

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Hepatobiliary Transport: From Bench to Bedside by S. Matern,J.L. Boyer,D. Keppler,P.J. Meier-Abt Pdf

There has been a tremendous amount of scientific progress in our understanding of the molecular mechanisms of transport processes in the liver within the last few years. Cloning of various members of organic anion and cation transporters has provided the necessary tools to study their regulation under physiological and pathophysiological conditions and has advanced our knowledge about bile formation. Mutations of various hepatic organic anion transporters have been identified in humans as hereditary defects leading to the heterogenous syndrome of progressive familial intrahepatic cholestasis (PFIC). Various mouse models including knockout animals have given us the opportunity to gain insight into lipid transport by the liver and the genetics of cholesterol gallstone formation. The physiology of bile duct cells and the molecular mechanisms leading to various cholangiopathies have been a main scientific focus in hepatology in recent years. Drug targeting to the liver by hepatic organic anion transporters represents an attractive way of selective delivery of pharmaceutical agents in humans. Ursodeoxycholic acid is successfully used in the treatment of patients with chronic cholestatic liver disease and major advances have been made in understanding its mode of action in liver and bile duct cells. This book, the proceedings of the Falk Workshop held in Aachen, Germany, on 25-26 January 2001, contains chapters on all important aspects of biliary transport by well-known experts in this field. It is an essential resource for new developments in the field of biliary transport, both in basic science and clinical medicine.

Drug Transporters

Author : Martin F. Fromm,Richard B. Kim
Publisher : Springer Science & Business Media
Page : 457 pages
File Size : 43,5 Mb
Release : 2010-11-19
Category : Medical
ISBN : 9783642145414

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Drug Transporters by Martin F. Fromm,Richard B. Kim Pdf

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

Drug Transporters

Author : Guofeng You,Marilyn E. Morris
Publisher : John Wiley & Sons
Page : 1012 pages
File Size : 55,5 Mb
Release : 2014-07-07
Category : Medical
ISBN : 9781118704981

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Drug Transporters by Guofeng You,Marilyn E. Morris Pdf

This new edition overviews drug transporters and presents the principles of drug transport and associated techniques, featuring new chapters on multidrug and toxin extrusion proteins, placental transport, in silico approaches in drug discovery, and regulatory guidance for drug transport studies in drug development. • Describes drug transporter families, mechanisms, and clinical implications along with experimental methods for studying and characterizing drug transporters • Includes new chapters on multidrug and toxin extrusion proteins, placental transport and in silico approaches in drug discovery • Has a new chapter covering regulatory guidance for the evaluation of drug transport in drug development with global criteria used for drug transporters in clinical trials • Arranges material to go from fundamental mechanisms to clinical outcomes, making the book useful for novice and expert readers

Drug Transporters

Author : Glynis Nicholls,Kuresh Youdim
Publisher : Royal Society of Chemistry
Page : 463 pages
File Size : 50,9 Mb
Release : 2016-08-16
Category : Science
ISBN : 9781782623793

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Drug Transporters by Glynis Nicholls,Kuresh Youdim Pdf

Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. In this first volume on Drug Transporters, the current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics are comprehensively reviewed. The second volume of the book is specifically dedicated to emerging science and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.

Textbook of Personalized Medicine

Author : Kewal K. Jain
Publisher : Humana Press
Page : 762 pages
File Size : 48,8 Mb
Release : 2015-03-17
Category : Medical
ISBN : 9781493925537

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Textbook of Personalized Medicine by Kewal K. Jain Pdf

Advances in the technology used in personalized medicine and increased applications for clinical use have created a need for this expansion and revision of Kewal K. Jain’s Textbook of Personalized Medicine. As the first definitive work on this topic, this book reviews the fundamentals and development of personalized medicine and subsequent adoptions of the concepts by the biopharmaceutical industry and the medical profession. It also discusses examples of applications in key therapeutic areas, as well as ethical and regulatory issues, providing a concise and comprehensive source of reference for those involved in healthcare management, planning and politics. Algorithms are included as a guide to those involved in the management of important diseases where decision-making is involved due to the multiple choices available. Textbook of Personalized Medicine, Second Edition will serve as a convenient source of information for physicians, scientists, decision makers in the biopharmaceutical and healthcare industries and interested members of the public.

Pharmacogenomics

Author : Julio Licinio,Ma-Li Wong
Publisher : John Wiley & Sons
Page : 599 pages
File Size : 52,9 Mb
Release : 2009-07-30
Category : Science
ISBN : 9783527616305

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Pharmacogenomics by Julio Licinio,Ma-Li Wong Pdf

This work represents the first comprehensive publication in the innovative field of pharmacogenomics, a field which is set to revolutionize pharmaceutical research. In addition to renowned editors, the list of contributors is a "who-is-who" in the field. Broad coverage of all aspects of pharmacogenomics with a full presentation of applications to disease conditions is featured. Anyone involved in pharmaceutical research and drug development needs this book to keep up with this new and revolutionary approach

Concepts in Pharmacogenomics

Author : Martin M. Zdanowicz
Publisher : ASHP
Page : 425 pages
File Size : 45,8 Mb
Release : 2010
Category : Medical
ISBN : 9781585282340

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Concepts in Pharmacogenomics by Martin M. Zdanowicz Pdf

The new science of pharmacogenomics aims to understand how an individual's genetic composition affects his/her response to a specific drug or class of drugs. By studying such characteristics as drug metabolizing enzymes, drug transporter activity, and receptor sensitivity, a pharmacist is better able to prescribe the right drug the first time.If you are pharmacist, resident, or student curious about this new field, start withConcepts in Pharmacogenomics. In this practical guide, you will find an overview of the science behind pharmacogenomics, followed by detailed chapters related to its clinical application and implementation.Features include: case studies in each chapter clinical pearls illustrations of key concepts figures, diagrams, and flow charts for visual learners key points summarized.

Human Drug Metabolism

Author : Michael D. Coleman
Publisher : John Wiley & Sons
Page : 688 pages
File Size : 43,7 Mb
Release : 2020-02-19
Category : Science
ISBN : 9781119458562

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Human Drug Metabolism by Michael D. Coleman Pdf

Provides a timely update to a key textbook on human drug metabolism The third edition of this comprehensive book covers basic concepts of teaching drug metabolism, starting from extreme clinical consequences to systems and mechanisms and toxicity. It provides an invaluable introduction to the core areas of pharmacology and examines recent progress and advances in this fast moving field and its clinical impact. Human Drug Metabolism, 3rd Edition begins by covering basic concepts such as clearance and bioavailability, and looks at the evolution of biotransformation, and how drugs fit into this carefully managed biological environment. More information on how cytochrome P450s function and how they are modulated at the sub-cellular level is offered in this new edition. The book also introduces helpful concepts for those struggling with the relationship of pharmacology to physiology, as well as the inhibition of biotransformational activity. Recent advances in knowledge of a number of other metabolizing systems are covered, including glucuronidation and sulphation, along with the main drug transporters. Also, themes from the last edition are developed in an attempt to chart the progress of personalized medicine from concepts towards practical inclusion in routine therapeutics. The last chapter focuses on our understanding of how and why drugs injure us, both in predictable and unpredictable ways. Appendix A highlights some practical approaches employed in both drug metabolism research and drug discovery, whilst Appendix B outlines the metabolism of some drugs of abuse. Appendix C advises on formal examination preparation and Appendix D lists some substrates, inducers and inhibitors of the major human cytochrome P450s. Fully updated to reflect advances in the scientific field of drug metabolism and its clinical impact Reflects refinements in the author's teaching method, particularly with respect to helping students understand biological systems and how they operate Illustrates the growing relationship between drug metabolism and personalized medicine Includes recent developments in drug discovery, genomics, and stem cell technologies Human Drug Metabolism, 3rd Edition is an excellent book for advanced undergraduate and graduate students in molecular biology, biochemistry, pharmacology, pharmacy, and toxicology. It will also appeal to professionals interested in an introduction to this field, or who want to learn more about these bench-to-bedside topics to apply it to their practice.

Pharmacogenomics in Drug Discovery and Development

Author : Qing Yan
Publisher : Springer Nature
Page : 618 pages
File Size : 52,9 Mb
Release : 2022-09-06
Category : Medical
ISBN : 9781071625736

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Pharmacogenomics in Drug Discovery and Development by Qing Yan Pdf

This new edition offers a state-of-the-art and integrative vision of pharmacogenomics by exploring new concepts and practical methodologies focusing on disease treatments, from cancers to cardiovascular and neurodegenerative disorders and more. The collection of these theoretical and experimental approaches facilitates problem-solving by tackling the complexity of personalized drug discovery and development. Written by leading experts in their fields for the highly successful Methods in Molecular Biology series, the book aims to provide across-the-board resources to support the translation of pharmacogenomics into better individualized health care. Authoritative and up-to-date, Pharmacogenomics in Drug Discovery and Development, Third Edition aims to aid researchers in approaching the challenges in pharmacogenomics and personalized medicine with the introduction of these novel ideas and cutting-edge methodologies.

Organic Cation Transporter 1 (OCT1): Not Vital for Life, but of Substantial Biomedical Relevance

Author : Jurgen Brockmoller,Mladen Vassilev Tzvetkov,Shuiying Hu
Publisher : Frontiers Media SA
Page : 145 pages
File Size : 45,7 Mb
Release : 2022-01-12
Category : Science
ISBN : 9782889740291

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Organic Cation Transporter 1 (OCT1): Not Vital for Life, but of Substantial Biomedical Relevance by Jurgen Brockmoller,Mladen Vassilev Tzvetkov,Shuiying Hu Pdf

Around one third of all biologically relevant small molecules are organic cations. These include endogenous substances like catecholamines and other neurotransmitters, toxins and drugs designed to affect signaling processes. The organic cation transporter 1 (OCT1) is among the strongest expressed membrane transporters at the sinusoidal (blood-facing) side of liver cells and contributes substantially to the clearance of the blood from numerous organic cations. A most striking feature of OCT1 is its pronounced genetic diversity. Between 1 and 10% of all human populations have little to no OCT1 activity. With several of the OCT1 substrates up to 10% of Europeans are functionally OCT1 deficient. Apparently, the lack of OCT1 do not lead to apparent substantial pathological changes in these individuals. It thus appears that this transporter is not essential to human life, but does it means that OCT1 is irrelevant? In the last 25 years since the first cloning of this transporter, data on its pharmacological and physiological relevance is steadily accumulating. Numerous clinically relevant drugs (e.g. metformin, morphine, fenoterol, sumatriptan, tramadol and tropisetron) have been shown to be substrates of OCT1, and OCT1 deficiency has been shown to affect the pharmacokinetics, efficacy, or toxicity of these drugs. Also vitamin B1 has been shown to be a substrate of OCT1, and in genetically modified mice OCT1 substantially modulated hepatic lipid metabolism, total body fat and systemic glucose and lipid concentrations. Still, numerous important questions remain unsolved: For which drugs, toxins, or other endogenous or exogenous substances is OCT1 relevant? How can we predict the relevance of OCT1 from in vitro studies? What determines the substrate selectivity of OCT1 in comparison to other transporters or transport processes for organic cations? What regulates the expression of OCT1 in the liver and possibly in other tissues? What is the impact of OCT1 variation in different areas of medicine, including the therapies for cancer as well as for pulmonary, cardiovascular, or neurological diseases? How can evolutionary biology contribute to a better understanding of the roles of OCT1? And, importantly, what types of research are likely to significantly further the knowledge on OCT1 in the next decades?

ABC Transporters - 40 Years on

Author : Anthony M. George
Publisher : Springer
Page : 376 pages
File Size : 47,5 Mb
Release : 2015-12-16
Category : Science
ISBN : 9783319234762

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ABC Transporters - 40 Years on by Anthony M. George Pdf

This book provides new structural, biochemical, and clinical information on ABC transporters. The authors explore and describe the state of the art of research, knowledge, and prospects for the future for this important family of proteins. The first ABC transporter was discovered in 1973 and was named P-glycoprotein. It elicits resistance to cytotoxic drugs, chiefly in human tumours, within which chemotherapy failure is observed in about 50% of cases. Together with its complex pharmacology, and even a suspected role in Alzheimer’s disease, this ABC transporter still eludes a clinical solution to its multidrug resistance property. ABC transporters are integral membrane active proteins and they belong to one of the largest protein families across all species. Their myriad roles encompass the import or export of a diverse range of allocrites, including ion, nutrients, peptides, polysaccharides, lipids, and xenobiotics. They are of major medical importance with many members elaborating multidrug resistance in bacteria, fungi, yeast, parasites, and humans. Other ABC transporters are involved in a number of inherited diseases, including cystic fibrosis, macular degeneration, gout, and several other metabolic disorders