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.
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.
As new techniques of transferring from liquid to gas phase and measuring masses of drug molecules and metabolites become more prevalent, so do the technical challenges of putting these techniques into proper use, as well as the task of consolidating emerging applications. Identification and Quantification of Drugs, Metabolites and Metabolizing Enzymes by LC-MS, Volume 6 fills the gap in the lack of presently available literature by providing a critical review in the current use of liquid chromatography-mass spectrometry (LC-MS) in drug discovery and development. With chapters written by experts with a wide range of practical experience from the pharmaceutical industry, emphasis is placed on techniques and applications. The book also includes chapters on how to utilize LC-MS instrumentation for current drug metabolism problems. This book is intended for those beginning to use LC-MS for drug metabolism studies as well as for those considered advanced practitioners.* Introduces readers to the practical applications of modern liquid chromatography-mass spectrometry (LC-MS) in a wide range of drug metabolism studies·* Provides a comprehensive description of different forms of metabolites, with detailed discussion on the wide range of methodologies used to identify them* Highlights problems associated with drug quantification and offers practical solutions
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.
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
Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint
Standard medicinal chemistry courses and texts are organized by classes of drugs with an emphasis on descriptions of their biological and pharmacological effects. This book represents a new approach based on physical organic chemical principles and reaction mechanisms that allow the reader to extrapolate to many related classes of drug molecules. The Second Edition reflects the significant changes in the drug industry over the past decade, and includes chapter problems and other elements that make the book more useful for course instruction. - New edition includes new chapter problems and exercises to help students learn, plus extensive references and illustrations - Clearly presents an organic chemist's perspective of how drugs are designed and function, incorporating the extensive changes in the drug industry over the past ten years - Well-respected author has published over 200 articles, earned 21 patents, and invented a drug that is under consideration for commercialization
Detection of Drugs and Their Metabolites in Oral Fluid presents the analytical chemistry methods used for the detection and quantification of drugs and their metabolites in human oral fluid. The authors summarize the state of the science, including its strengths, weaknesses, unmet methodological needs, and cutting-edge trends. This volume covers the salient aspects of oral fluid drug testing, including specimen collection and handling, initial testing, point of collection testing (POCT), specimen validity testing (SVT), and confirmatory and proficiency testing. Analytes discussed include amphetamines, cannabinoids, cocaine, opiates, phencyclidine, cannabimimetics, and miscellaneous drugs. This practical guide helps users turn knowledge into practice, moving logically from an outline of the problem, to the evaluation of the appropriateness of oral fluid as a test medium, and finally to a consideration of detection methods and their validation and employment. - Compares different collection and testing systems to assist readers involved in clinical or forensic practice in selecting oral fluid as the matrix of choice - Provides a sound basis for the detection of drugs and their metabolites in oral fluid and the interpretation of both positive and negative - Places the need, or lack thereof, for specimen validity testing and confirmation testing in context with the purposes of oral fluid testing - Describes drugs and drug classes that can be tested, along with useful information on a patient/donor's drug status
Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.
