Human Drug Metabolism

The book provides an exhaustive, authoritative and updated review on the interindividual variability in drug metabolism in humans. Four chapters address the general background: genetic factors causing variability, interethnic variability, environmental factors and developing and ageing as sources of variability. Six chapters address variability of drug metabolism in vivo: variability of psychotropic drugs, antiepileptic drugs, the dopamine precursor levodopa, cardiovascular active drugs and anti HIV drugs. Seven chapters address the interindividual variability of the main drug metabolizing enzymes: CYP-450s, acetyltransferases, glucuronosyl transferase, methyl transferases, sulfotransferases and glutathione transferases in human liver and extrahepatic tissues. A separate chapter discusses the prediction of drug interaction. Comprehensive in coverage, and with contributions from the leading international experts, this book is essential reading for researchers from both academia and the pharmaceutical industry. Advanced undergraduates and postgraduates in pharmacology, clinical pharmacology, toxicology, biochemistry and epidemiology who are interested in drug metabolism will also find this an indispensable resource.

Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences. Completely revised and updated throughout, the new edition focuses only on essential chemical detail and includes patient case histories to illustrate the clinical consequences of changes in drug metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration, both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.

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.

Variability in Human Drug Response examines why individual patients differ significantly in their response to drug administration. This book is devoted mainly to pharmacokinetics and covers topics such as drug absorption, distribution, metabolism, and excretion. The sensitivity of tissues of the body to drugs and the importance of monitoring drug therapy are also discussed. This book is comprised of 10 chapters and begins with an introduction to variability in clinical response to administration of defined drugs, as well as the importance of closely matching dosage to the individual patient's requirement to achieve an optimal response to drug administration. The chapters that follow highlight the pharmacokinetic origin of most variability in the clinical response to drugs, along with the difficulties inherent in predicting the effect of drug administration in an individual patient. The role of genetic and environmental factors, disease, and the concomitant administration of other drugs in determining an individual's response to any therapeutic maneuver is also examined. The last chapter describes two methods of monitoring drug therapy: monitoring drug effects or monitoring the plasma levels of drugs. This monograph will be of interest to practicing clinicians and senior medical students.

Drug Metabolism and Pharmacokinetics Quick Guide covers a number of aspects of drug assessment at drug discovery and development stages, topics such as pharmacokinetics, absorption, metabolism, enzyme kinetics, drug transporters, drug interactions, drug-like properties, assays and in silico calculations. It covers key concepts, with useful tables on physiological parameters (eg. blood flow to organs in x-species, expression and localization of enzymes and transporters), chemical structure, nomenclature, and moieties leading to bioactivation (with examples). Overall it includes a number of key topics useful at the drug discovery stage, which would serve as a quick reference with several examples from the literature to illustrate the concept.

A practice-oriented desktop reference for medical professionals, toxicologists and pharmaceutical researchers, this handbook provides systematic coverage of the metabolic pathways of all major classes of xenobiotics in the human body. The first part comprehensively reviews the main enzyme systems involved in biotransformation and how they are orchestrated in the body, while parts two to four cover the three main classes of xenobiotics: drugs, natural products, environmental pollutants. The part on drugs includes more than 300 substances from five major therapeutic groups (central nervous system, cardiovascular system, cancer, infection, and pain) as well as most drugs of abuse including nicotine, alcohol and "designer" drugs. Selected, well-documented case studies from the most important xenobiotics classes illustrate general principles of metabolism, making this equally useful for teaching courses on pharmacology, drug metabolism or molecular toxicology. Of particular interest, and unique to this volume is the inclusion of a wide range of additional xenobiotic compounds, including food supplements, herbal preparations, and agrochemicals.

Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters, Second Edition, is completely updated to provide an overview of the last decade's numerous advances in analytical technologies for detection and quantification of drugs, metabolites, and biomarkers. This new edition goes beyond LC-MS and features all-new chapters on how to evaluate drug absorption, distribution, metabolism, and excretion, potential for hepatic and renal toxicity, immunogenicity of biotherapeutics and translational tools for predicting human dosage, safety and efficacy of small molecules and biologics. This book will be an important handbook and desk reference for pharmacologists, toxicologists, clinical scientists, and students interested in the fields of pharmacology, biochemistry, and drug metabolism. Four sections in the book with 24 chapters give readers an overview of state-of-the-art techniques for identifying and quantifying drugs, metabolites and biomarkers, including a chapter on new approaches for quantification of enzymes and transporters in different tissues Focuses on the role of drug metabolism enzymes, transporters in disposition and drug-drug interactions, as well as strategies for evaluating drug metabolism and safety using advanced liver and kidney models. Discussions on immunogenicity risks of biologics and their evaluation methods have been included Includes several chapters on advanced translational sciences to predict human dosage, pharmacokinetics and efficacy for small molecules and biotherapeutics All chapters are written by experts with a wide range of practical experience from the industry and academia