Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing monooxygenases (FMO) are covered. Moreover, the book deals with genotoxicity studies and toxicological interactions of environmental chemicals and mechanisms of mutagenicity and tumor formation. The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. Further, insight is provided into how a number of aquatic species cope with pollutants and their genotoxicity.
Written by leading researchers in the fields of biochemistry, molecular biology, genetics, pharmacology, toxicology, biotechnology and cancer, this is a comprehensive update on molecular biology and biochemistry of cytochromes P450 and flavin containing monoxygenases. The volume provides expert analysis of the genetic polymorphism of these enzymes in the clinic, in drug discovery and development, and discussion of their role in predisposition for, and prevention of chemical carcinogens in humans.
Drug metabolism and transport are very important facets within the discipline of pharmaceutical sciences, with enzyme kinetic concepts utilized regularly in characterizing and modeling the disposition and elimination of drugs. Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications focuses on very practical aspects of applying kinetic principles to drug metabolizing enzymes and transporters. Divided into five convenient sections, topics include the fundamental principles of enzyme kinetics, the kinetics of oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for both drug metabolizing enzymes and transporters including novel systems biology approaches, understanding of variability both experimental and interindividual (pharmacogenomic), and case studies that provide real life examples of applying these principles. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics especially suitable for the novice, in some cases step-by-step, readily reproducible protocols, and insights to help with troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and easily accessible, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications serves as a very practical teaching tool for novice, non-mathematically trained scientists interested in these fundamental concepts and as an aid for their supervisors in teaching these principles.
Microsomes and Drug Oxidations is a record of the proceedings of the Third International Symposium on Microsomes and Drug Oxidations, held in Berlin, Germany in July 1976. The compendium provides an overview of knowledge on the oxidative metabolism of drugs, carcinogens, and various other environmental chemicals. Topics discussed include lipid structure of liver microsomal membranes; interactions between cytochrome p-450 and nadphcytochrome p-450 reductase in the microsomal membrane; impact of drug monoxygenases in clinical pharmacology; and the manner in which oxygen participates in mixed-function oxidation reactions. Pharmacologists, toxicologists, biochemists, and researchers in the pharmaceutical industry will find the book highly insightful.
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.
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.
This revised second edition covers the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development, focusing on the fundamentals that underlie the clinical use and contemporary development of pharmaceuticals. Authors drawn from academia, the pharmaceutical industry and government agencies cover the spectrum of material, including pharmacokinetic practice questions, covered by the basic science section of the certifying examination offered by the American Board of Clinical Pharmacology. This unique reference is recommended by the Board as a study text and includes modules on drug discovery and development to assist students as well as practicing pharmacologists. - Unique breadth of coverage ranging from drug discovery and development to individualization and quality assessment of drug therapy - Unusual cohesive of presentation that stems from author participation in an ongoing popular NIH course - Instructive linkage of pharmacokinetic theory and applications with provision of sample problems for self-study - Wide-ranging perspective of authors drawn from the ranks of Federal agencies, academia and the pharmaceutical industry - Expanded coverage of pharmacogenetics - Expanded coverage of drug transporters and their role in interactions - Inclusion of new material on enzyme induction mechanisms in chapters on drug metabolism and drug interactions - A new chapter on drug discovery that focuses on oncologic agents - Inclusion of therapeutic antibodies in chapter on biotechnology products
A comprehensive guide to cutting-edge tools in ADME research The last decade has seen tremendous progress in the development of analytical techniques such as mass spectrometry and molecular biology tools, resulting in important advances in drug discovery, particularly in the area of absorption, distribution, metabolism, and excretion (ADME). ADME-Enabling Technologies in Drug Design and Development focuses on the current state of the art in the field, presenting a comprehensive review of the latest tools for generating ADME data in drug discovery. It examines the broadest possible range of available technologies, giving readers the information they need to choose the right tool for a given application, a key requisite for obtaining favorable results in a timely fashion for regulatory filings. With over thirty contributed chapters by an international team of experts, the book provides: A thorough examination of current tools, covering both electronic/mechanical technologies and biologically based ones Coverage of applications for each technology, including key parameters, optimal conditions for intended results, protocols, and case studies Detailed discussion of emerging tools and techniques, from stem cells and genetically modified animal models to imaging technologies Numerous figures and diagrams throughout the text Scientists and researchers in drug metabolism, pharmacology, medicinal chemistry, pharmaceutics, toxicology, and bioanalytical science will find ADME-Enabling Technologies in Drug Design and Development an invaluable guide to the entire drug development process, from discovery to regulatory issues.
Haschek and Rousseaux's Handbook of Toxicologic Pathology is a key reference on the integration of structure and functional changes in tissues associated with the response to pharmaceuticals, chemicals and biologics. The 3e has been expanded by a full volume, and covers aspects of safety assessment not discussed in the 2e. Completely revised with many new chapters, it remains the most authoritative reference on toxicologic pathology for scientists and researchers studying and making decisions on drugs, biologics, medical devices and other chemicals, including agrochemicals and environmental contaminants. New topics include safety assessment, the drug life cycle, risk assessment, communication and management, carcinogenicity assessment, pharmacology and pharmacokinetics, biomarkers in toxicologic pathology, quality assurance, peer review, agrochemicals, nanotechnology, food and toxicologic pathology, the environment and toxicologic pathology and more. - Provides new chapters and in-depth discussion of timely topics in the area of toxicologic pathology and broadens the scope of the audience to include toxicologists and pathologists working in a variety of settings - Offers high-quality and trusted content in a multi-contributed work written by leading international authorities in all areas of toxicologic pathology - Features hundreds of full color images in both the print and electronic versions of the book to highlight difficult concepts with clear illustrations
