Reactive Drug Metabolites

A comprehensive review of current thinking on the biosynthesis, function and evolution of secondary metabolites in animals, plants and microorganisms. Examines the traditional context of secondary metabolites as natural products having no obvious part to play in the producing organism's life cycle. Covers issues related to genetic and antibiotic applications.

Plant secondary metabolites have been a fertile area of chemical investigation for many years, driving the development of both analytical chemistry and of new synthetic reactions and methodologies. The subject is multi-disciplinary with chemists, biochemists and plant scientists all contributing to our current understanding. In recent years there has been an upsurge in interest from other disciplines, related to the realisation that secondary metabolites are dietary components that may have a considerable impact on human health, and to the development of gene technology that permits modulation of the contents of desirable and undesirable components. Plant Secondary Metabolites: Occurrence, Structure and Role in the Human Diet addresses this wider interest by covering the main groups of natural products from a chemical and biosynthetic perspective with illustrations of how genetic engineering can be applied to manipulate levels of secondary metabolites of economic value as well as those of potential importance in diet and health. These descriptive chapters are augmented by chapters showing where these products are found in the diet, how they are metabolised and reviewing the evidence for their beneficial bioactivity.

Drug-Drug Interactions in Pharmaceutical Development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage.

Strategize, plan, and execute comprehensive drug-drug interaction assessments for therapeutic biologics Offering both theory and practical guidance, this book fully explores drug-drug interaction assessments for therapeutic biologics during the drug development process. It draws together and analyzes all the latest findings and practices in order to present our current understanding of the topic and point the way to new research. Case studies and examples, coupled with expert advice, enable readers to better understand the complex mechanisms of biologic drug-drug interactions. Drug-Drug Interactions for Therapeutic Biologics features contributions from leading international experts in all areas of therapeutic biologics drug development and drug-drug interactions. The authors' contributions reflect a thorough review and analysis of the literature as well as their own firsthand laboratory experience. Coverage includes such essential topics as: Drug-drug interaction risks in combination with small molecules and other biologics Pharmacokinetic and pharmacodynamic drug-drug interactions In vitro methods for drug-drug interaction assessment and prediction Risk-based strategies for evaluating biologic drug-drug interactions Strategies to minimize drug-drug interaction risk and mitigate toxic interactions Key regulations governing drug-drug interaction assessments for therapeutic biologics. Drug-Drug Interactions for Therapeutic Biologics is recommended for pharmaceutical and biotechnology scientists, clinical pharmacologists, medicinal chemists, and toxicologists. By enabling these readers to understand how therapeutic biologics may interact with other drugs, the book will help them develop safer, more effective therapeutic biologics.

DRUG TRANSPORTERS [b]Drug transporter fundamentals and relevant principles and techniques, featuring new and expanded chapters Drug Transporters: Molecular Characterization and Role in Drug Disposition provides in-depth analysis of the conceptual evolution and technical development for studying drug transporters. Contributions by an international panel of leading researchers address advances in transporters as drug targets, transporters in pharmacotherapy, the impact of transporters on drug efficacy and safety, the development of sophisticated model systems and sensitive assay methods, and more. Divided into two parts, the book first provides a thorough overview of relevant drug transporters before detailing the principles of drug transport and associated techniques. The updated and expanded third edition includes new chapters on in vitro-in vivo scale-up of drug transport activities, the ontogeny of drug transporters, the application of physiologically-based pharmacokinetic and pharmacodynamic modeling, and the use of transporters as therapeutic targets for diseases. Reflects the current state of the field and offers perspectives on future directions Covers basic knowledge, clinical outcomes, and emerging discoveries in transporter science Provides up-to-date information on drug transporter families, mechanisms, and clinical implications Includes extensive references and numerous figures and tables throughout Understandable for novices while offering sufficient depth for more experienced researchers, Drug Transporters: Molecular Characterization and Role in Drug Disposition, Third Edition is an excellent textbook for pharmacological or physiological science courses in drug/membrane transport, and an invaluable reference for academic or industrial scientists working in the transporter field and related areas of drug metabolism, pharmacokinetics, and pharmacodynamics.

Sets forth the history, state of the science, and future directions of drug discovery Edited by Jie Jack Li and Nobel laureate E. J. Corey, two leading pioneers in drug discovery and medicinal chemistry, this book synthesizes great moments in history, the current state of the science, and future directions of drug discovery into one expertly written and organized work. Exploring all major therapeutic areas, the book introduces readers to all facets and phases of drug discovery, including target selection, biological testing, drug metabolism, and computer-assisted drug design. Drug Discovery features chapters written by an international team of pharmaceutical and medicinal chemists. Contributions are based on a thorough review of the current literature as well as the authors' firsthand laboratory experience in drug discovery. The book begins with the history of drug discovery, describing groundbreaking moments in the field. Next, it covers such topics as: Target identification and validation Drug metabolism and pharmacokinetics Central nervous system drugs In vitro and in vivo assays Cardiovascular drugs Cancer drugs Each chapter features a case study, helping readers understand how science is put into practice throughout all phases of drug discovery. References at the end of each chapter serve as a gateway to groundbreaking original research studies and reviews in the field. Drug Discovery is ideal for newcomers to medicinal chemistry and drug discovery, providing a comprehensive overview of the field. Veterans in the field will also benefit from the perspectives of leading international experts in all aspects of drug discovery.

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.

Written by a leading authority with an excellent reputation and ability for writing a good narrative, Drug Discovery: A History is a far cry from simply a list of chemical structures. This lively new text considers the origins, development and history of medicines that generate high media interest and have a huge social and economic impact on society. Set within a wide historical, social and cultural context, it provides expanded coverage of pre-twentieth century drugs, the huge advances made in the twentieth century and the latest developments in drug research. Hallmark features: Up-to-the-minute information in drug research Vignettes of special and unusual information, and anecdotes Discusses drug prototypes from all sources More comprehensive than other volumes on history of drug discovery From the reviews: «…an excellent bibliographic resource for those interested in the background papers that serve as the foundation for discovery of specific drug entities.» JOURNAL OF MEDICAL CHEMISTRY, June 2006 «…a very comprehensive overview of drug development. It should be on the shelf on any aspiring pharmacist, medicinal chemist, or person interested in the history of therapeutic agents.» JOURNAL OF CHEMICAL EDUCATION, February 2006 «…a very readable and closely researched book…» CHEMISTRY & INDUSTRY, October 2005

The book «Drug Selectivity – An Evolving Concept in Medicinal Chemistry» provides a current overview and comprehensive compilation for medicinal chemists that discusses the effects of aiming for multiple targets on the entire drug development process. The result is a broad survey of current and future strategies for drug selectivity in medicinal chemistry with theoretical but also practical aspects. Different strategies are presented and evaluated, such as various design approaches, merged multiple ligands, discovery technologies and a broad range of successful examples of unselective drugs taken from all major disease areas. With its wide-ranging view of an emerging new paradigm in drug development, this handbook is of prime importance for every medicinal and pharmaceutical chemist.

The gold standard for industrial research now completely revised in line with current trends in the field, with all contributions extensively updated or rewritten. In 21 chapters readers can benefit from the key working knowledge of today's leading pharmaceutical companies, including Pfizer, AstraZeneca, and Roche. Drug developers from industry and academia present all the factors governing drug bioavailability, complete with practical examples and real-life data. Part I focuses on in vitro and in vivo measurements of physicochemical properties, such as membrane permeability and ionization. Part II discusses solubility and gastrointestinal absorption, while the third part is devoted to metabolism and excretory mechanisms. The much revised and expanded part IV surveys current in silico approaches to predict drug properties needed to estimate the bioavailability of any new drug candidate. The final part shows how poor bioavailability may be improved by various approaches during the development process. No other publication offers the same level of treatment on this crucial topic in modern drug development.