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Stable isotope techniques offer advantages in safety, sensitivity, specificity, and economy for many types of pharmaceutical investigations when compared to conventional techniques. Nevertheless, pharmaceutical researchers are slow to embrace stable isotope techniques. This book assembles in one place comprehensive reviews of the many applications of stable isotopes and the background material necessary to understand the application. This approach is a deliberate attempt to encourage the usage of stable isotopes in pharmaceutical research. A bonus to the reader is the high standard of contributions from a very talented and diverse group of investigators.
Radioactive isotopes and enriched stable isotopes are used widely in medicine, agriculture, industry, and science, where their application allows us to perform many tasks more accurately, more simply, less expensively, and more quickly than would otherwise be possible. Indeed, in many casesâ€"for example, biological tracersâ€"there is no alternative. In a stellar example of "technology transfer" that began before the term was popular, the Department of Energy (DOE) and its predecessors has supported the development and application of isotopes and their transfer to the private sector. The DOE is now at an important crossroads: Isotope production has suffered as support for DOE's laboratories has declined. In response to a DOE request, this book is an intensive examination of isotope production and availability, including the education and training of those who will be needed to sustain the flow of radioactive and stable materials from their sources to the laboratories and medical care facilities in which they are used. Chapters include an examination of enriched stable isotopes; reactor and accelerator-produced radionuclides; partnerships among industries, national laboratories, and universities; and national isotope policy.
Radioactive isotopes and enriched stable isotopes are used widely in medicine, agriculture, industry, and science, where their application allows us to perform many tasks more accurately, more simply, less expensively, and more quickly than would otherwise be possible. Indeed, in many casesâ€"for example, biological tracersâ€"there is no alternative. In a stellar example of "technology transfer" that began before the term was popular, the Department of Energy (DOE) and its predecessors has supported the development and application of isotopes and their transfer to the private sector. The DOE is now at an important crossroads: Isotope production has suffered as support for DOE's laboratories has declined. In response to a DOE request, this book is an intensive examination of isotope production and availability, including the education and training of those who will be needed to sustain the flow of radioactive and stable materials from their sources to the laboratories and medical care facilities in which they are used. Chapters include an examination of enriched stable isotopes; reactor and accelerator-produced radionuclides; partnerships among industries, national laboratories, and universities; and national isotope policy.
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
The use of Compound-specific Stable Isotope Analysis (CSIA) is increasing in many areas of science and technology for source allocation, authentication, and characterization of transformation reactions. Until now, there have been no textbooks available for students with an analytical chemical background or basic introductory books emphasising the instrumentation and theory. This book is the first to focus solely on stable isotope analysis of individual compounds in sometimes complex mixtures. It acts as both a lecture companion for students and a consultant for advanced scientists in fields including forensic and environmental science. The book starts with a brief history of the field before going on to explain stable isotopes from scratch. The different ways to express isotope abundances are introduced together with isotope effects and isotopic fractionation. A detailed account of the required technical equipment and general procedures for CSIA is provided. This includes sections on derivatization and the use of microextraction techniques in GC-IRMS. The very important topic of referencing and calibration in CSIA is clearly described. This differs from approaches used in quantitative analysis and is often difficult for the newcomer to comprehend. Examples of successful applications of CSIA in food authenticity, forensics, archaeology, doping control, environmental science, and extraterrestrial materials are included. Applications in isotope data treatment and presentation are also discussed and emphasis is placed on the general conclusions that can be drawn from the uses of CSIA. Further instrumental developments in the field are highlighted and selected experiments are introduced that may act as a basis for a short practical course at graduate level.
This publication contains a collection of 22 manuscripts by authors invited to write review articles. They are based on lectures presented on the First and Second Training Course in Radiopharmacy and Radiopharmacology. These courses were organized under the auspices of the "Joint Committee on Radiopharmaceuticals" of both European Societies of Nuclear Medicine (ENMS and SNME) and were sponsored by the European Society of Nuclear Medicine (ENMS). Recent developments in radiopharmacy and radiopharmacology have been very complex; they cannot be overlooked by the medical staff in nuclear medical departments. This book has been written to provide access to recent research and to practical daily routine in patients' investigations. It provides a wide-ranging and topical overview of radiopharmacology in­ cluding chapters on basic chemistry and physics, incorporation dosimetry, interference of drugs in radiopharmacokinetics, legal aspects and stable isotope-labelled pharmaceuticals. Style of presentation is not uniform. Par­ tial overlapping concerning the content of papers has not been avoided in order to ensure different views and aspects of the same subject. We hope that the interdisciplinary approach will be stimulating and thought-provok­ ing for the reader. Consequently, this book is designed for specialists work­ ing in nuclear medical centres which involve different disciplines such as pharmacists, radiochemists, physicists, biochemists, biologists, mathemati­ cians, electronic engineers, physicians with different specialities, and tech­ nicians.
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.