Download or read book Reactive Drug Metabolites written by Amit S. Kalgutkar and published by John Wiley & Sons. This book was released on 2012-09-06 with total page 445 pages. Available in PDF, EPUB and Kindle. Book excerpt: Closing a gap in the scientifi c literature, this first comprehensive introduction to the topic is based on current best practice in one of the largest pharmaceutical companies worldwide. The first chapters trace the development of our understanding of drug metabolite toxicity, covering basic concepts and techniques in the process, while the second part details chemical toxicophores that are prone to reactive metabolite formation. This section also reviews the various drug-metabolizing enzymes that can participate in catalyzing reactive metabolite formation, including a discussion of the structure-toxicity relationships for drugs. Two chapters are dedicated to the currently hot topics of herbal constituents and IADRs. The next part covers current strategies and approaches to evaluate the reactive metabolite potential of new drug candidates, both by predictive and by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustrating the power and the limits of the toxicophore concept, backed by numerous case studies. Finally, a risk-benefi t approach to managing the toxicity risk of reactive metabolite-prone drugs is presented. Since the authors carefully develop the knowledge needed, from fundamental considerations to current industry standards, no degree in pharmacology is required to read this book, making it perfect for medicinal chemists without in-depth pharmacology training.
Download or read book Adverse Drug Reactions written by Jack Uetrecht and published by Springer Science & Business Media. This book was released on 2009-12-18 with total page 552 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the current state of knowledge of basic mechanisms of adverse drug reactions (ADRs). The main focus is on idiosyncratic drug reactions because they are the most difficult to deal with. It starts with a general description of the major targets for ADRs followed by a description of what are presently believed to be mediators and biochemical pathways involved in idiosyncratic drug reactions. There is also a description of several examples of ADRs that serve to illustrate specific aspects of ADR mechanisms. Eventually the book shows that ultimately better methods are needed to predict which drug candidates are likely to cause ADRs and which patients are at increased risk. But at present research seems to be far from this goal.
Download or read book Drug Metabolism written by Jack P. Uetrecht and published by CRC Press. This book was released on 2007-06-20 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: In order to understand drug metabolism at its most fundamental level, pharmaceutical scientists must be able to analyze drug compound structure and predict possible metabolic pathways in order to avoid the risk of adverse reactions that lead to the withdrawal of a drug from the market. This title is a comprehensive guide for recognizing the chemica
Download or read book Metabolite Safety in Drug Development written by Suzanne L. Iverson and published by John Wiley & Sons. This book was released on 2016-07-05 with total page 351 pages. Available in PDF, EPUB and Kindle. Book excerpt: A reference on drug metabolism and metabolite safety in the development phase, this book reviews the analytical techniques and experimental designs critical for metabolite studies. It features case studies of lessons learned and real world examples, along with regulatory perspectives from the US FDA and EMA. • Reviews the analytical techniques and experimental designs critical for metabolite studies • Covers methods including chirality, species differences, mass spectrometry, radiolabels, and in vitro / in vivo correlation • Discusses target pharmacology, in vitro systems aligned to toxicity tests, and drug-drug interactions • Includes perspectives from authors with firsthand involvement in industry and the study of drug metabolites, including viewpoints that have influenced regulatory guidelines
Download or read book Transporters and Drug Metabolizing Enzymes in Drug Toxicity written by Albert P. Li and published by John Wiley & Sons. This book was released on 2021-07-27 with total page 530 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Involvement of Reactive Metabolites in Idiosyncratic Drug Reactions written by and published by . This book was released on 2003 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: PhD.
Download or read book Drug Metabolism in Drug Design and Development written by Donglu Zhang and published by John Wiley & Sons. This book was released on 2007-11-16 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Drug Induced Liver Toxicity written by Minjun Chen and published by Humana Press. This book was released on 2018-03-21 with total page 667 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive view of the methodologies used for the study of liver toxicity encountered throughout the whole life cycle of a drug, from drug discovery, to clinical trial, post-marketing, and even clinical practice. Organized into six sections, the first section introduces the mechanisms contributing to drug-induced liver toxicity. The second and third section explore in silico and in vitro approaches used to help mitigate hepatotoxicity liability at the early stages of drug development. The fourth section describes methodologies applied in regulatory processes, including preclinical studies, clinical trials, and post-marketing surveillance. The fifth section discusses clinical hepatotoxicity. Emerging technologies are examined in the final section. As a volume in the Methods in Pharmacology and Toxicology series, chapters include the kind of expert advice that will lead to optimal results. Authoritative and practical, Drug-Induced Liver Toxicity serves all those who aim to improve assessment and understanding of hepatotoxic potentials of new medications and marketed drugs. Chapter 30 is open access under a CC BY 4.0 license via link.springer.com.
Download or read book Pharmacokinetics and Metabolism in Drug Design written by Dennis A. Smith and published by John Wiley & Sons. This book was released on 2012-05-14 with total page 269 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this new edition of a bestseller, all the contents have been brought upto-date by addressing current standards and best practices in the assessment and prediction of ADMET properties. Although the previous chapter layout has been retained, substantial revisions have been made, with new topics such as pro-drugs, active metabolites and transporters covered in detail in a manner useful to the Drug Discovery scientist. The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. While aimed at all those dealing professionally with the development and application of pharmaceutical substances, the readily comprehensible style makes this book equally suitable for students of pharmacy and related subjects. Uniquely comprehensive, the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety.
Download or read book Involvement of Reactive Metabolites in Idiosyncratic Drug Reactions written by Mukundan Baskar Mannargudi and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Idiosyncratic drug reactions (IDRs) represent a significant medical problem and pose a great challenge to drug development. Circumstantial evidence suggests that, in most cases, reactive metabolites of the drug are responsible. The major focus of this thesis is the identification of reactive metabolites and the synthesis of analogs required to test several hypotheses related to involvement of metabolism and covalent binding in the mechanisms of IDRs. D-penicillamine is known to cause idiosyncratic autoimmune reactions in humans. The goal of this project was to test whether D-penicillamine covalently binds to macrophages and triggers downstream events leading to autoimmunity. To test a part of this hypothesis, D-penicillamine conjugated to biotin was synthesized. In summary, reactive metabolites of minocycline were found that likely explain why minocycline has an IDR profile unique among the tetracyclines. In addition, analogs of nevirapine and D-penicillamine required for mechanistic studies of nevirapine and D-penicillamine-induced IDRs were synthesized. These studies provide additional support for the involvement of reactive metabolites in the mechanisms of IDRs. Nevirapine, an anti-HIV drug, is associated with idiosyncratic skin rashes in humans. The goal of this project was to investigate whether the 12-hydroxylation pathway is responsible for the skin rash. To test a part of this hypothesis, 12-trideuteronevirapine, 12-OH-NVP sulfate, and several other analogs of nevirapine were synthesized. Minocycline is unique among tetracyclines in causing a significant incidence of a lupus-like syndrome and autoimmune hepatitis. In this study, we demonstrated that minocycline is oxidized to reactive intermediates by myeloperoxidase/H 2O2/Cl-, HOCl, horseradish peroxidase/H 2O2, or hepatic microsomes. When trapped with N-acetylcysteine (NAC), two adducts with protonated molecular ions at m/z 619 were isolated and analyzed by NMR. One represents attack of the aromatic D ring by NAC meta to the N, N-dimethylamino group, implying that the reactive intermediate was a quinone iminium ion. The other adduct, which was not observed when minocycline was oxidized by hepatic microsomes, indicates that the NAC is attached at the junction of the B and C rings, suggesting that the HOCl added across the double bond of the B ring leading to a reactive molecule, and then NAC displaced the chloride ion.
Download or read book Drug Metabolism Handbook written by Ala F. Nassar and published by John Wiley & Sons. This book was released on 2009-01-28 with total page 1059 pages. Available in PDF, EPUB and Kindle. Book excerpt: A valuable reference tool for professionals involved in the industry, Drug Metabolism in Pharmaceuticals covers new tools such as LC-MS and LC-MS-NMR along with experimental aspects of drug metabolism. This work fills a gap in the literature by covering the concepts and applications of pharmaceutical research, development, and assessment from the point of view of drug metabolism. By providing both a solid conceptual understanding of the drug metabolism system, and a well illustrated, detailed demonstration and explanation of cutting edge tools and techniques, this book serves as a valuable reference tool for bench scientists, medical students, and students of general health sciences.
Download or read book Drug Metabolism Handbook written by Ala F. Nassar and published by John Wiley & Sons. This book was released on 2022-11-18 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive explanation of drug metabolism concepts and applications in drug development and cancer treatment In the newly revised second edition of Drug Metabolism Handbook: Concepts and Applications in Cancer Research, a distinguished team of researchers delivers an incisive and robust exploration of the drug metabolism system and a well-illustrated and detailed explanation of the latest tools and techniques used in the research, pharmacology, and medicine. The book discusses the creation of new molecular entities, drug development, troubleshooting, and other highly relevant concepts, guiding readers through new applications in pharmaceutical research, development, and assessment. The latest edition offers updated content on metabolism basics and the application of a variety of new techniques to cancer treatment, including mass spectrometry, imaging, metabolomics, and immunotherapy. It also offers in-depth case studies highlighting the role of metabolism in drug development. Readers will also benefit from: A thorough introduction to drug metabolism, including a historical perspective, factors affecting metabolism, and biotransformations in drug metabolism Comprehensive discussions of technologies for in vitro and in vivo studies, including mass spectrometry and accelerating metabolite identification with mass spectrometry In-depth explorations of drug interactions, including discussions of enzyme inhibition and the characterization of cytochrome P450 mechanism-based inhibition Fulsome treatments of drug toxicity, including the role of drug metabolism in toxicity, and allergic reactions to drugs Perfect for medicinal chemists, pharmaceutical scientists, and toxicologists, Drug Metabolism Handbook: Concepts and Applications in Cancer Research, Second Edition will also earn a place in the libraries of analytical chemists and drug discovery professionals.
Download or read book Pharmaceuticals from Microbes written by Divya Arora and published by Springer. This book was released on 2019-02-12 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book deals with the noteworthy advancement in the production of bioactive metabolites from microbes and their pharmacological significance. It highlights the pharmacological potential of marine microbes and endophytic fungi and their bioactive secondary metabolites. Emphasis is also given on the significance of probiotics and their specialized molecules in human health and disease as well as their role in dietary intervention for reducing the risk of non-alcoholic fatty liver disease. This work also serves as excellent reference material for researchers, students and academicians in the field of natural product chemistry, pharmacology and applied microbiology.
Download or read book Reactive Drug Metabolites written by Jørgen Olsen and published by . This book was released on 2002 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mass Spectrometry in Drug Metabolism and Disposition written by Mike S. Lee and published by John Wiley & Sons. This book was released on 2011-03-16 with total page 648 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines the background, industrial context, process, analytical methodology, and technology of metabolite identification. It emphasizes the applications of metabolite identification in drug research. While primarily a textbook, the book also functions as a comprehensive reference to those in the industry. The authors have worked closely together and combine complementary backgrounds to bring technical and cultural awareness to this very important endeavor while serving to address needs within academia and industry It also contains a variety of problem sets following specific sections in the text.
Download or read book Mechanisms of Drug Toxicity written by H. Rašková and published by Elsevier. This book was released on 2013-10-22 with total page 113 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mechanisms of Drug Toxicity, Volume 4 presents the proceedings of the 3rd International Pharmacological Meeting held in Sao Paulo, Brazil in 1966. The book discusses the drug-induced pathobiotic effects; the mechanisms of adverse reactions; and enzyme induction in the mechanism of chronic toxicity. The text also describes the influence of inducing substances on the growth of liver and microsomal electron transport systems; the quantitative aspects of chronic toxicity; and the facts and fallacies in predicting drug effects in human.
Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
