Circadian Pharmacokinetics


Book Description

This book summarizes the recent advances for the understanding of circadian clock system in the regulation of drug metabolism and pharmacokinetics. Basic knowledge in the field of circadian clock and pharmacokinetics are systemically introduced to make it easier for readers to understand the entire book's contents. The rhythmic expression of DMEs (drug-metabolizing enzymes) and transporters are summarized, and the underlying mechanisms thereof (i.e., regulation by circadian oscillators) are discussed. Typically, evidence for the DME- and transporter-mediated chronopharmacokinetics, chronotoxicity and chronoefficacy are highlighted in this book.




Holland-Frei Cancer Medicine


Book Description

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




Circadian Rhythms and Metabolism


Book Description

One of the major breakthroughs of the last decade in the understanding of energy homeostasis is the identification of a reciprocal control between circadian rhythmicity and cellular metabolism. Circadian rhythmicity is a fundamental endogenous process of almost every organism living on Earth. For instance, the alternation of hunger and satiety is not continuous over 24 h, but is instead structured in time along the light/dark cycle. In mammals, the temporal organization of metabolism, physiology and behavior around 24 h is controlled by a network of multiple cellular clocks, synchronized via neuronal and hormonal signals by a master clock located in the suprachiasmatic nuclei of the hypothalamus. This central circadian conductor in the brain is mainly reset by ambient light perceived by the retina, while secondary circadian clocks in other brain areas and peripheral organs can be reset by meal timing. Chronic disruption of circadian rhythms, as seen in human shift-workers (up to 20% of the active population), has been associated with the development of a number of adverse mental and metabolic conditions. Understanding of the functional links between circadian desynchronization and overall health in animal models and humans, however, is still scarce. Interactions between circadian clocks and metabolism can occur at different levels: the molecular clockwork, internal synchronization via neuro-hormonal signals, or external synchronization via photic or feeding cues. This Research Topic comprises a number of reviews as well as research and methods articles that feature recent advancements in the mechanisms linking circadian clocks with energy metabolism, and the pathophysiological implications of these interactions for metabolic health.




Chronotherapeutics


Book Description

In nature, many physical processes are governed by the passage of time. The study of these processes - chronobiology - reveals rhythmic patterns which may be yearly, monthly, daily or more frequent. Novel drug delivery systems are currently being delivered that will release varying quantities of a drug at optimum times to coincide with these rhythmic patterns.Chronotherapeutics considers the pharmaceutical and therapeutic implications associated with biological clocks. The book presents a comprehensive discussion of specific diseases that are time dependent, and the drugs and new drug formulations that can be used as treatments.Written by leading international experts in the field, Chronotherapeutics provides up-to-date information on chronobiology for non-chronobiologists in pharmaceutical and medical sciences. Peter Redfern is Professor of Pharmacology at the University of Bath, UK.




Biopharmaceutics and Pharmacokinetics Considerations


Book Description

Biopharmaceutics and Pharmacokinetics Considerations examines the history of biopharmaceutics and pharmacokinetics. The book provides a biopharmaceutics and pharmacokinetics approach to addressing issues in formulation development and ethical considerations in handling animals. Written by experts in the field, this volume within the Advances in Pharmaceutical Product Development and Research series deepens understanding of biopharmaceutics and pharmacokinetics within drug discovery and drug development. Each chapter delves into a particular aspect of this fundamental field to cover the principles, methodologies and technologies employed by pharmaceutical scientists, researchers and pharmaceutical industries to study the chemical and physical properties of drugs and the biological effects they produce. - Examines the most recent developments in biopharmaceutics and pharmacokinetics for pharmaceutical sciences - Covers the principles, methodologies and technologies of biopharmaceutics and pharmacokinetics - Focuses on the pharmaceutical sciences, but also encompasses aspects of toxicology, neuroscience, environmental sciences and nanotechnology




Military Strategies for Sustainment of Nutrition and Immune Function in the Field


Book Description

Every aspect of immune function and host defense is dependent upon a proper supply and balance of nutrients. Severe malnutrition can cause significant alteration in immune response, but even subclinical deficits may be associated with an impaired immune response, and an increased risk of infection. Infectious diseases have accounted for more off-duty days during major wars than combat wounds or nonbattle injuries. Combined stressors may reduce the normal ability of soldiers to resist pathogens, increase their susceptibility to biological warfare agents, and reduce the effectiveness of vaccines intended to protect them. There is also a concern with the inappropriate use of dietary supplements. This book, one of a series, examines the impact of various types of stressors and the role of specific dietary nutrients in maintaining immune function of military personnel in the field. It reviews the impact of compromised nutrition status on immune function; the interaction of health, exercise, and stress (both physical and psychological) in immune function; and the role of nutritional supplements and newer biotechnology methods reported to enhance immune function. The first part of the book contains the committee's workshop summary and evaluation of ongoing research by Army scientists on immune status in special forces troops, responses to the Army's questions, conclusions, and recommendations. The rest of the book contains papers contributed by workshop speakers, grouped under such broad topics as an introduction to what is known about immune function, the assessment of immune function, the effect of nutrition, and the relation between the many and varied stresses encountered by military personnel and their effect on health.




Physiology and Pharmacology of Biological Rhythms


Book Description

Measured by any criteria, research in chronobiology in general and chronopharmacology in particular has expanded rapidly in recent years. This expansion has been paralleled by an increasing recognition by those outside the field of the relevance and significance of recent developments in chronobiology. Advances in two areas have been chiefly responsible. First, application of the full range of modern techniques in behavioral, neurochemical, and molecular biology have greatly improved our understanding of basic clock mechanisms. In several species the genetic basis of the circadian clock is being progressively delineated. A complete picture of the neurochemical and neuroanatomical structure of the mammalian clock is emerging and the complex pattern of control mechanisms involving endogenous clock mechan isms and photic and nonphotic zeitgebers is being built up as a result of behavioral studies. Secondly, in parallel with these exciting developments in basic science, clinical applications are being convincingly demonstrated in the general fields of pharmacology and medicine as well as in specific areas, e.g., jet lag, shiftwork maladaption syndrome, blindness, and cardiovascular system. It is therefore an opportune time to review progress in the field of chronopharmacology and to introduce some of the exciting developments and prospects to a readership beyond the confines of the chronobiological cognoscenti. This volume is therefore aimed primarily at the pharmacologist - whether basic, applied, or clinical-who is not a specialist in chronobiology.




Circadian Clocks


Book Description

This book provides the reader with a contemporary and comprehensive overview about the molecular, cellular and system-wide principles of circadian clock regulation. Emphasis is placed on the importance of circadian clocks for the timing of therapeutic interventions.




Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays


Book Description

Many aspects of drug safety have become an outstanding and even persistent issue and may occur during the process of both drug discovery and development. Until 15 years ago, drug discovery and evaluation was primarily a sequential process starting with the selection of the most pharmacologically active compound from a series of newly synthesized small molecule chemical series by means of distinctive pharmacological assays. Safety aspects were addressed by evaluation of the selected compound at high doses in a series of specific studies directed at indications other than the intended indication of the new compound. These tests are then followed by pharmacokinetic studies, which are primarily conducted to confirm whether the selected compound possesses a suitable half-life for sufficient exposure and efficacy and, whether it has the desired properties specificity to the intended route of administration. Safety aspects relied predominantly on the conduct of single and repeat toxicologydose studies, which inform changes in organ structure rather than organ function. Both toxicological and pharmacokinetic studies are adapted to the progress of studies in clinical pharmacology and clinical trials. The new edition of this well and broadly accepted reference work contains several innovative and distinguished chapters. This "sequential" strategy has been abandoned with this new version of the book for several reasons: - Of the possible multitude of negative effects that novel drugs may impart on organ function, e.g. ventricular tachy-arrhythmia, many are detected too late in non-clinical studies to inform clinicians. On the other hand, negative findings in chronic toxicity studies in animals may turn out to be irrelevant for human beings. - New scientific approaches, e.g. high-throughput screening, human pluripotent stem cells, transgenic animals, knock-out animals, in silico models, pharmaco-genomics and pharmaco-proteomics, as well as Artificial Intelligence (AI) methods offered new possibilities. - There are several examples, that show that the "druggability" of compounds was considerably underestimated when the probability of success of a new project was assessed. The success rate in the pharmaceutical industry and the introduction of new chemical entities to the market per year dropped dramatically, whereas the development time for a new compound increased, sometimes exceeding the patent protection. Research and development scientists, involving the following changes, therefore adopted a change of strategy: - Parallel instead of sequential involvement of the various disciplines (multidimensional compound optimization). - The term "Safety Pharmacology" was coined. The International Conference on Harmonization (ICH) founded a Safety Pharmacology Working Group and the Safety Pharmacology Society (SPS) was launched. The discipline provided for evaluation, development and validation of a multitude of safety tests outlined in the 'Core Battery of Studies'. - Characterizing the exposure profile of a drug by conducting pharmacokinetic studies that evaluates the absorption, distribution, metabolism and excretion should to be investigated at an early stage of development as results contribute to the selection of a compound for further development. Advancements in Toxicology were achieved by the introduction of new methods, e.g., in silico methods, genetic toxicology, computational toxicology and AI. The book is a landmark in the continuously changing world of drug research and developments. As such, it is essential reading for many groups: not only for all students of pharmacology and toxicology but also for industry scientists and physicians, especially those involved in clinical trials of drugs, and for pharmacists who must know the safety requirements of drugs. The book is essential for scientists and managers in the pharmaceutical industry who are involved in drug discovery, drug development and decision making in the development process. In particular, the book will be of use to government institutions and committees working on official guidelines for drug evaluation worldwide.




Chronopharmacology


Book Description

Chronopharmacology is the study of time-dependent variations in the pharmacokinetics, effects, and side and toxic effects of drugs. After three chapters on basic aspects, the remaining 46 contributions cover various types of drugs and discuss the regulatory issues related to circadian mechanisms and the predictive aspects of the science. Annotation(c) 2003 Book News, Inc., Portland, OR (booknews.com)




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