Advanced Issue Resolution In Safety Pharmacology

Advanced Issue Resolution in Safety Pharmacology not only discusses unique issues that may emerge during the development of new medicines, but also provides detailed insights on how to resolve them. The book employs a valuable strategy that integrates preclinical findings with the clinical resolution of those findings. In addition, it introduces key interdisciplinary topics in an accessible and systematic format. Edited and written by leaders in the field of safety pharmacology, this book considerably advances the discussion on issue resolution topics, thus raising them to the next level of importance by providing scientists with an indispensable resource on solving safety issues. Focuses on pharmacology issues that result during drug development and provides de-risking techniques and practical advice Covers a broad selection of topics, including specialized animal models, PBPK modeling, the use of high frequency EEG in problem-solving, drug-induced self-injury, abuse potential liability, biomarkers, imaging, and much more Focuses on the resolution of these issues in order to better address regulatory expectancies and develop safer, more effective drugs

This book illustrates, in a comprehensive manner, the most current areas of importance to Safety Pharmacology, a burgeoning unique pharmacological discipline with important ties to academia, industry and regulatory authorities. It provides readers with a definitive collection of topics containing essential information on the latest industry guidelines and overviews current and breakthrough topics in both functional and molecular pharmacology. An additional novelty of the book is that it constitutes academic, pharmaceutical and biotechnology perspectives for Safety Pharmacology issues. Each chapter is written by an expert in the area and includes not only a fundamental background regarding the topic but also detailed descriptions of currently accepted, validated models and methods as well as innovative methodologies used in drug discovery.

Hayes’ Principles and Methods of Toxicology has long been established as a reliable and informative reference for the concepts, methodologies, and assessments integral to toxicology. The new edition contains updated and new chapters with the addition of new authors while maintaining the same high standards that have made this book a benchmark resource in the field. Key Features: The comprehensive yet concise coverage of various aspects of fundamental and applied toxicology makes this book a valuable resource for educators, students, and professionals. Questions provided at the end of each chapter allow readers to test their knowledge and understanding of the material covered. All chapters have been updated and over 60 new authors have been added to reflect the dynamic nature of toxicological sciences New topics in this edition include Safety Assessment of Cosmetics and Personal Care Products, The Importance of the Dose/Rate Response, Novel Approaches and Alternative Models, Epigenetic Toxicology, and an Expanded Glossary. The volume is divided into 4 major sections, addressing fundamental principles of toxicology (Section I. "Principles of Toxicology"), major classes of established chemical hazards (Section II. "Agents"), current methods used for the assessment of various endpoints indicative of chemical toxicity (Section III. "Methods"), as well as toxicology of specific target systems and organs (Section IV. "Organ- and System-Specific Toxicology"). This volume will be a valuable tool for the audience that wishes to broaden their understanding of hazards and mechanisms of toxicity and to stay on top of the emerging methods and concepts of the rapidly advancing field of toxicology and risk assessment.

Burger’s Medicinal Chemistry, Drug Discovery and Development Explore the freshly updated flagship reference for medicinal chemists and pharmaceutical professionals The newly revised eighth edition of the eight-volume Burger’s Medicinal Chemistry, Drug Discovery and Development is the latest installment in this celebrated series covering the entirety of the drug development and discovery process. With the addition of expert editors in each subject area, this eight-volume set adds 35 chapters to the extensive existing chapters. New additions include analyses of opioid addiction treatments, antibody and gene therapy for cancer, blood-brain barrier, HIV treatments, and industrial-academic collaboration structures. Along with the incorporation of practical material on drug hunting, the set features sections on drug discovery, drug development, cardiovascular diseases, metabolic diseases, immunology, cancer, anti-Infectives, and CNS disorders. The text continues the legacy of previous volumes in the series by providing recognized, renowned, authoritative, and comprehensive information in the area of drug discovery and development while adding cutting-edge new material on issues like the use of artificial intelligence in medicinal chemistry. Included: Volume 1: Methods in Drug Discovery, edited by Kent D. Stewart Volume 2: Discovering Lead Molecules, edited by Kent D. Stewart Volume 3: Drug Development, edited by Ramnarayan S. Randad and Michael Myers Volume 4: Cardiovascular, Endocrine, and Metabolic Diseases, edited by Scott D. Edmondson Volume 5: Pulmonary, Bone, Immunology, Vitamins, and Autocoid Therapeutic Agents, edited by Bryan H. Norman Volume 6: Cancer, edited by Barry Gold and Donna M. Huryn Volume 7: Anti-Infectives, edited by Roland E. Dolle Volume 8: CNS Disorders, edited by Richard A. Glennon Perfect for research departments in the pharmaceutical and biotechnology industries, Burger’s Medicinal Chemistry, Drug Discovery and Development can be used by graduate students seeking a one-stop reference for drug development and discovery and deserves its place in the libraries of biomedical research institutes, medical, pharmaceutical, and veterinary schools.

In this eBook, we have grouped together 16 original contributions which have addressed the translational potential for therapeutics developed on the conceptual framework of the resolution of inflammation. The take home message of our effort, and the efforts of our colleagues who wrote these pieces, is that completely different drugs can be designed and modelled on the mediators and targets of resolution. By implementing this 180° shift in the way we plan the drug development programme (that is by focusing on agonists and/or promoting the actions of pro-resolution agonists) we can offer a fresh approach to the clinical management of chronic diseases that affect the modern society. With this series of articles we foresee the birth of Resolution Pharmacology. The 16 contributions presented herein confirm the broad relevance of pro-resolving physio-pharmacology with the description of pro-resolving mechanisms in distinct diseases, from atherosclerosis and heart infarct, to cystic fibrosis and diabetes. This testifies on one hand the fundamental role that inflammatory mechanisms play in virtually all pathological settings and, on the other hand, the great potential that a novel approach to anti-inflammatory therapy by exploiting resolution mediators and targets may have. Thus, while there is broad recognition that evidence-based interventions have transformed cardiovascular, inflammation and endocrine care, new therapies are still needed for growing numbers of patients with unmet needs. As an example, an estimated 17 million people world-wide die annually of cardiovascular diseases, particularly heart attacks and strokes. Cardiovascular diseases occur almost equally in men and women and are the leading cause of death and morbidity worldwide. It is estimated that only 1/1,000 compounds entering preclinical testing are then trialled in man and the actual cost of developing a new therapeutic into clinical practice has grown exponentially over the past two decades (estimated $1.2B). Over the last 20 years or more, scientists have appreciated the biology of the resolution of inflammation, which provides a new paradigm in our understanding of the inflammatory process with the appreciation of genetic, molecular and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the host reaction while at the same time promoting healing and repair. The potential of lipid mediators to enact pro-resolving effects in the context of cystic fibrosis is presented by Recchiuti et al., while Fredman reasons on the potential for these molecules in atherosclerosis. This resonates well with the contributions from Bäck and colleagues who have focused on pro-resolving receptors to offer vasculo-protection in intimal hyperplasia and more generally in cardiovascular disease. On the same vein is the scholar contribution of Leoni and Soehnlein who focus on heart disease, with Qin et al. presenting the latest findings on the effect of an Annexin A1-derived peptide in myocardial infarction. Hansen et al. and de Gaetano et al. bring in the complexity of diabetes and associated morbidity with a focus on specialised pro-resolving lipid mediators but also introducing the potential of dietary approaches. As the western diet favours disease, an omega-3 rich diet can lead to higher availability of lipid mediators to afford tissue protection if not reverting its pathological status. Docosahexaenoic acid and its bioactive derivatives are endowed with potent anti-nociceptive properties following bone fracture, as shown by Zhang et al. The broad relevance of the pharmacological approach reaches the skin with Resolvin D1 protecting against UV irradiation (Saito et al.). Reduced skin inflammation is also achieved with an Annexin A1 peptide that impacts on the outcome of heterologous transplantation (Lacerda et al.). Indeed, modulating the phenotype of immune cells can provide long lasting beneficial outcomes, as attained with CDK inhibitors (Cartwright et al.) and PI3K inhibitors in experimental gout (Galvao et al.). Such an effect is also achieved with a third group of pro-resolving therapeutics, the melanocortin receptor agonists, with important modulation of macrophage reactivity (Patruno et al.) with Spana et al., providing new pharmacology following selective activation of the MC1 receptor. Finally, Hopkin et al. discuss the potential for targeting immune cell trafficking as a way to control immune mediated diseases, bringing in not only pro-resolving mediator agonists, but also approaches to reduce chemo/cytokine gradients or modulating S1P and 11-beta hydroxysteroid dehydrogenase. Finally, we wish to highlight that this wealth of science has also bought to the forefront specific pro-resolving receptors (including FPR2/ALX, GPR32, ChemR23 and MC1), all G protein coupled receptors that are therefore amenable to pharmacological exploitation for drug discovery programmes. We see that not only agonists to the receptors can be developed, some of them modelled on the natural ligands (e.g. resolvins, lipoxins, Annexin A1-derived peptides or melanocortin peptides), but also that the creativity of this pharmacology can be attained through biased ligands and positive allosteric modulators. Deep knowledge of pro-resolving receptor biology and their cell-specific signalling can accelerate the generation of novel anti-inflammatory depicted on the resolution of inflammation. In conclusion, with this eBook, we propose time is ready to exploit the concepts of resolution and use its targets and mediators for the identification of better drugs to establish ‘Resolution Pharmacology’. We predict Resolution Pharmacology will represent an important innovation in the way common diseases will be treated in the next decades of this millennium.

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

-A landmark in the continuously changing world of drugs -Essential reading for scientists and managers in the pharmaceutical industry involved in drug finding, drug development and decision making in the development process -Of use for government institutions and committees working on official guidelines for drug evaluation worldwide

Nanoparticles as both potential unique risks and as a valuable approach to increased and higher specificity in delivery of therapeutics A primer on the largest, most diverse, and important microbiome in any mammal "Tricks of the trade" on modifying the oral administration of drugs