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.

Founded on the paradox that all things are poisons and the difference between poison and remedy is quantity, the determination of safe dosage forms the base and focus of modern toxicology. In order to make a sound determination there must be a working knowledge of the biologic mechanisms involved and of the methods employed to define these mechanisms. While the vastness of the field and the rapid accumulation of data may preclude the possibility of absorbing and retaining more than a fraction of the available information, a solid understanding of the underlying principles is essential. Extensively revised and updated with four new chapters and an expanded glossary, this fifth edition of the classic text, Principles and Methods of Toxicology provides comprehensive coverage in a manageable and accessible format. New topics include 'toxicopanomics', plant and animal poisons, information resources, and non-animal testing alternatives. Emphasizing the cornerstones of toxicology-people differ, dose matters, and things change, the book begins with a review of the history of toxicology and followed by an explanation of basic toxicological principles, agents that cause toxicity, target organ toxicity, and toxicological testing methods including many of the test protocols required to meet regulatory needs worldwide. The book examines each method or procedure from the standpoint of technique and interpretation of data and discusses problems and pitfalls that may be associated with each. The addition of several new authors allow for a broader and more diverse treatment of the ever-changing and expanding field of toxicology. Maintaining the high-quality information and organizational framework that made the previous editions so successful, Principles and Methods of Toxicology, Fifth Edition continues to be a valuable resource for the advanced practitioner as well as the new disciple of toxicology.

Handbook of Radioactivity Analysis is written by experts in the measurement of radioactivity. The book describes the broad scope of analytical methods available and instructs the reader on how to select the proper technique. It is intended as a practical manual for research which requires the accurate measurement of radioactivity at all levels, from the low levels encountered in the environment to the high levels measured in radioisotope research. This book contains sample preparation procedures, recommendations on steps to follow, necessary calculations, computer controlled analysis, and high sample throughput techniques. Each chapter includes practical techniques for application to nuclear safety, nuclear safeguards, environmental analysis, weapons disarmament, and assays required for research in biomedicine and agriculture. The fundamentals of radioactivity properties, radionuclide decay, and methods of detection are included to provide the basis for a thorough understanding of the analytical procedures described in the book. Therefore, the Handbook can also be used as a teaching text. - Includes sample preparation techniques for matrices such as soil, air, plant, water, animal tissue, and surface swipes - Provides procedures and guidelines for the analysis of commonly encountered na

Although there are numerous books on drug metabolism, Radiotracers in Drug Development is unique in explaining how radiotracers are used to elucidate a drug's absorption, distribution, metabolism, and excretion (ADME). Covering traditional and recent technologies and applications, the book takes a strong industrial approach, discussing the b

The topics chosen for this volume were selected because they are some of the current development or technological issues facing drug development project teams. They regard the practical considerations for assessment of selected special development populations. For example, they include characterization of drug disposition in pregnant subjects, for measuring arrhythmic potential, for analysis tumor growth modeling, and for disease progression modeling. Practical considerations for metabolite safety testing, transporter assessments, Phase 0 testing, and development and execution of drug interaction programs reflect current regulatory topics meant to address enhancement of both safety assessment and early decision-making during new candidate selection. Important technologies like whole body autoradiography, digital imaging and dried blood spot sample collection methods are introduced, as both have begun to take a more visible role in pharmacokinetic departments throughout the industry.

This book describes levels of autoradiography, which is the localization within a solid specimen of a radiolabel, to help the beginner or biologist choose the correct approach for particular application. It attempts to lay emphasis on certain aspects of the appraisal of autoradiographs.

Autoradiography has been used only to a rather limited extent in metallurgical studies. Probably the major deterring factor has been that the autoradiographic systems have not provided the high resolution required in many investigations. A general discussion of the requirements for high-resolution autoradiography is presented in this report including detecting layer as well as radioactive-sample specifications. The need for a thin photographic emulsion in close contact with the metal surface is emphasized. The desirability of using favorable radiation (e.g., low-energy beta radioactivity) is also discussed.

The focus of this new book is for medicinal chemists on the chemical agents that have been used, or might be required in the future, and the methods of synthesis for inserting the reporter groups. Medicinal chemists need to know the critical issues involved in using such chemical agents with regard to the biological applications - for instance - what properties are needed chemically and why? The topics covered in the book are: PET, SPECT, contrast agents, radioimaging/radionuclide conjugates, receptor mapping, small animal imaging (eg. WBAR - whole body autoradiography); photoinduced labelling, as well as chapters on the physical techniques used including: NMR, mass spectrometry and Xray. A key reference for academics, postgraduates, researchers, industrialists and professionals working in or joining this field.

This volume is a comprehensive introduction to the analysis, binding, uptake, metabolism, kinetics, modeling, distribution, occurrence, toxicity and chelation of metals and fluoride in the body, with special reference to mineralized tissues. Both toxic and relatively harmless polyvalent cations and anions are considered. Included are some which are stable, and others which are radioactive. While a number are essential trace elements, others have no known metabolic role. Most chapters are concerned with the uptake of bone-seeking ions by the living skeleton, but aspects of the post-mortem uptake of metals and the process of fossilization are also considered. Highlighted are the utility of modern analytical techniques and the more important bone-seeking elements including aluminum, lead, cadmium, fluorine and the radioactive heavy metals including uranium and plutonium. This important publication is of particular value to those in the fields of biochemistry, radioactive waste, geology, physiology, dentistry, orthopedics, radiology and nuclear medicine, urology, industrial hygiene, pharmacology, anthropology, paleontology, and archeology.