Protein and peptide therapeutics currently represent eight of the top 100 prescription pharmaceuticals in the U.S., and biotechnology products are projected to account for 15% of the total US. prescription drug market by 2003. Of the protein and peptide products now on the market, many are administered as daily injections, though several are deliveredby noninvasive routes. For example, desmopressin is delivered as a nasal spray, and deoxyribonuclease I is administered by inhalation. Although cyclosporin A is orally active, as yet there are no general means to confer oral bioava- ability to peptides and proteins. A major advance in delivery ofpeptides was achieved with the introduction of a monthly injectable, biodegradable microsphere formulation of LHRH. Despite the enormous success of biotechnology products to date, much effort continues to be focused on the development of more convenient and noninvasive routes of administration for those products that require f- quent and prolonged dosing. Here we present an overview of the te- nologies, both developed and emerging, which are applicable to protein delivery. In addition, chapters 11 through 13 detail case studies on physical methods for delivery ofinsulin and growth hormone

This volume attemptsto provide the formulation scientist with casehistories involving the use of therapeutic proteins and peptides that have been mar- keted or are under clinical testing. In previous volumes of this series,funda- mental theories and principles ofprotein characterization and stability were presented in depth by researchers in their fieldsofexpertise. The way from theory to practice isnot alwaysobvious and straightforward. There isa need for practical examples of how the principles and theories are put into use, specificallyin the development of a pharmaceutical product. It is our hope that this volume will fulfillsuch a need. Itisnot asimple task to choose a panel ofproteinsand peptides from the over 200 agents in human clinical trials. We have tried to collect a wide representation of molecules of different sizes-from 10 amino acids (Leu- prolide) to 1020 amino acids (Muromonab CD3). The examples include agents derived from various sources including monoclonal antibodies (Mur- omonab CD3), recombinant DNA (human and bovine growth hormones), natural source (fibrolase), and chemical synthesis (Leuprolide). Clearly this list is not intended to be encyclopedic. It isthe first time a collection of this sort has been made accessibleto the formulation scientists involved in devel- oping protein and peptide products. Although each chapter in this volume focuses primarily on the charac- terization and stability of a specific molecule, each has unique aspects.

The first book was on "Theory and Practice" of antibiotic stewardship in its broadest sense -the how to do it and the do's and don'ts. The second, on "Controlling resistance" was very much on the relationships between use and resistance and beginning to home in on the hospital as the main generator of resistance, but mainly looking at it from a disease/clinical perspective. The last 3 chapters on MRSA, ended where the 3rd book will take off. "Controlling HAI " will concentrate on specific MDR organisms highlighting their roles in the current pandemic of HAI and emphasizing that the big issue is not so much infection control but antibiotic control, in the same way that antibiotic over-reliance/ over-use has caused the problem in the first place. Up 'till now the emphasis for controlling MRSA, C diff and all the other MDROs has very much been on IC, which clearly isn't working. This book will gather all the evidence for the increasingly popular view that much more must be done in the area of antibiotic policies/ stewardship, especially when we are in danger of a "post antibiotic" era, due to a real shortage of new agents in the pipeline.

Over the past 50 years, more than 100,000 scientific papers, not to mention popular articles and books, have been written about Selenium. These publications continue to appear without showing any sign of diminution today. This mass of writing makes it very difficult for anyone, who is not a dedicated and specialized scientist, to get a clear picture of what is now known about the element and its role in human health. The second edition of Selenium in Food and Health takes into account the considerable amount of fresh information that has been published over the past decade, by investigators from a wide range of specialties, not all of which, at first glance, might appear to have much to do with human health. It presents information in an easy-to-follow manner for the general reader who wants to make an informed judgment about the competing claims for and against Selenium's value as a nutritional supplement,

This volume provides an up-to-date account of the achievements pertaining to the application of capsaicin and capsaicin-like molecules in the therapy of various human ailments such as pain, non-allergic rhinitis, obesity, tumors and gastrointestinal, dermatologic and urologic disorders. It discusses the basic functionsof the capsaicin receptor (TRPV1), its mechanisms of action and its role in physiological and pathological processes. The text focuses on the most recent progress in the use of capsaicin and capsaicin-like molecules as a therapeutic agent and highlights potential pharmaceutical implications of further TRPV1 research. The chapters are written by noted experts in their fields of endeavor. This book offers both clinicians and researchers valuable resource and reference material on the subject that will stimulate future research. "

At a time when it is becoming usual for medicines to be developed for a global market and pharmaceutical companies are endeavouring to expedite the drug development process, Regulatory authorities are concentrating on improving their efficiency and effectiveness. Therefore, it is not surprising that questions are being asked as to how performance might be measured and compared between different authorities who are now often in receipt of dossiers that have been submitted to several agencies at the same time. Issues such as "what target should be set for the review of new medicines?" and "how can quality be assured?" are now considered to be of critical importance. The 12th CMR International Workshop, held in January 1997, provided the opportunity for regulatory authority and industry personnel from Europe, North America, Australia and Japan to openly discuss experiences and exchange views on how to improve the review process. The proceedings of this meeting provide a comprehensive overview of the current review process in different countries and the need for performance measures and targets. This volume summarizes the many suggestions that were debated at the workshop, and includes chapters on measuring performance, and on the integration of quality into the review process.

The principal objective of this symposium was to bring together investigators from all over the world who work in diverse areas of research but share a common interest in the physiologic and pathophysiologic funetions of the nueleoside adenosine. In 1978, the "International Conference on Physiological and Regulatory Funetions of Adenosine and Adenine Nueleotides," held in Banff, Canada, served as an effective catalyst in enabling scientists with differ ent points of view to exchange information and ideas on this subject. Since 1978, the amount of research on different as peets of adenosine metabolism, mechanism of action, transport, and function in various tissues (in both nor maI and abnormal states) has increased exponentially, and there was an urgent need for another meeting for updating information on this burgeoning subject. The focus of the meeting was extremely sharp, but the scope of the subject material was very broad. Scientists categorized as chemists, biochemists, physiologists, pharmacologists, and immunologists, working with cells and eelI fragments, with tissues such as heart, brain, musele, fat, kidney, and with human beings having immune deficiency diseases participated in the sym posium. They had an opportunity to air their differences, reinforce their areas of agreement, and, most important, they educated each other with respeet to research on adenosine; it is hoped that they also enriched their own research programs from the information they gained from their fellow participants."

Volumes in this widely revered series present comprehensive reviews of drug substances and additional materials, with critical review chapters that summarize information related to the characterization of drug substances and excipients. This organizational structure meets the needs of the pharmaceutical community and allows for the development of a timely vehicle for publishing review materials on this topic.
The scope of the Profiles series encompasses review articles and database compilations that fall within one of the following six broad categories: Physical profiles of drug substances and excipients; Analytical profiles of drug substances and excipients; Drug metabolism and pharmacokinetic profiles of drug substances and excipients; Methodology related to the characterization of drug substances and excipients; Methods of chemical synthesis; and Reviews of the uses and applications for individual drug substances, classes of drug substances, or excipients.

Key features:

* Contributions from leading authorities * Informs and updates on all the latest developments in the field

Comprehensive and state of the art, the second edition of Pharmacotherapy of Depression offers major revisions of every chapter and the addition of new chapters by expert contributors. The first chapter reviews the neurobiology of depression, which lays the groundwork for understanding the mechanisms of action of antidepressants. In the next chapter, a review of the general principles guiding the diagnosis and medication treatment of unipolar depression is provided. The clinical pharmacology of antidepressants is reviewed in some detail, supplemented by tables that provide information on dosing, indications, and metabolism. Augmentation strategies are reviewed, including the use of non-traditional agents. The chapters that follow next address the use of antidepressants in special populations, such as the elderly and depressed individuals with psychosis, bipolar disorder, substance abuse, and post traumatic stress disorder. The complex issues involving the diagnosis and treatment of depression during pregnancy is thoroughly reviewed in Chapter 8 and provides a synthesis of the scientific literature in the area, one that is noted for contradictory and controversial findings, as well as guidelines for prescribing. The next chapter then provides an overview of the treatment of depression in the pediatric population, highlighting clinical concerns such as suicide risk. The book concludes with two chapters at the interface of medicine and psychiatry in the treatment of mood disorders: managing depression in primary care settings and depression associated with medical illnesses. The outstanding clinician-scientists who have contributed to this volume are all leaders in their fields and represent a broad spectrum of renowned institutions. A timely contribution to the literature, The Pharmacotherapy of Depression, Second Edition, offers busy clinicians from many disciplines a strong scientific foundation that seamlessly transitions into practical recommendations for clinical practice. The result is another gold-standard guide to the safe and effective use of the latest antidepressant medications.

This book is composed of four major sections: The perception of risk, where authorities from the field of environmental psychology and risk analysis describe the backgrounds and mechanisms of cognitive behavior and the effects of emotional and publicity factors on perception and acceptance of risk. The management of infection-defined risk, the core of public and political anxiety. Here the book illustrates how safe the current blood supply has become over the past decade in at least the majority of industrialized countries in the world. The management of immune-defined risks has been the Cinderella of blood transfusion and transfusion medicine up till now. Risk management in clinical practice: optimal versus maximal is the section where the real virtue of reality comes to life through valuable contributors by authors from the field of clinical blood banking, heavily involved consumers organizations (WFH), the Cochrane Institute of Medical Sciences and National Health Services Center for reviews and dissemination, and international policy makers and regulative bodies like the Council of Europe and the European Commission. When the reader is first confronted with a poem illustrating the reality of virtue, written by one of the editors noted for his talent in anecdotal medical poetry, the scene is set for the virtue of reality in the management of risk in blood transfusion.

This volume comprises papers presented at the 40th Erice Course "From Molecules to Medicine: Structure of Biological Macromolecules and Its Relevance in Combating New Diseases and Bioterrorism," May 29 to June 8, 2008. The papers span the breadth of material presented, which emp- size the practical aspects of modern macromolecular crystallography and its applications to medicine. Topics addressed span from the selection of targets, through to structure determination, interpretation and exploitation. A particular theme that emerges is the dependence of modern structural science on multiple experimental and computational techniques. It is both the development of these techniques and their integration that will take us forward in the future. The NATO ASI directors worked alongside, and offer deep gratitude to Prof. Sir Tom Blundell, Director of the International School of Crystal- graphy, Dr Colin Groom, Dr Neera Borkakoti, Dr John Irwin and Prof. Lodovico Riva di Sanseverino, who were in turn supported by a number of local facilitators. The course was financed by NATO as an Advanced Study Institute. Additional support was given by the European Crystallographic Association, the International Union of Biochemistry and Molecular Biology, the Int- national Union of Crystallography, the University of Bologna, AstraZeneca, Roche, Merck & Co., Boehringer Ingelheim, Bruker Corporation, Douglas Instruments, Informa UK, the Department of Pharmaceutical Chemistry, TTP Lab Tech, University of California at San Francisco. Joel L. Sussman and Paola Spadon

Clinical Pharmacology During Pregnancy, Second Edition is written for clinicians, physicians, midwives, nurses, pharmacists and other medical professionals involved in the care of women during pregnancy. The book focuses on the impact of pregnancy on drug disposition and includes coverage of treatments for diseases of specific body systems as well as essential content on dosing and efficacy. This update includes substantially expanded sections on the ethics of pharmacological research in pregnancy and physiologic changes, along with new sections on patient reported outcomes in pregnancy, delivery and postnatal care, and the use of pharmacokinetic and pharmacodynamic approaches to estimate maternal, placental and fetal dosing. The broad range of this book encompasses analgesics, antiasthmatics, antidepressants, heart and circulatory drugs, vitamins and herbal supplements, and more. Topics in chemotherapy and substance abuse are also covered, as are research issues, including clinical trial design and ethical considerations.

This book explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences.

If the antibody industry is to achieve its full potential in the next decade, the individual technical potentials must be exploited, the limitations must be addressed, and lessons learned must be applied both to current purification methods and to the new technologies that continue to emerge. This book presents an overview of the current advances applied in the manufacture of monoclonal antibody including:
-concepts in development of manufacturing strategies,
-importance of antibody fragments,
-application of chromatography method development,
-quality control,
-effect of expression on antibody properties,
-virus removal and safety,
-pharmacokinetics,
-regulatory aspects.

Antibodies Volume 1: Production and Purification together with Volume 2: Novel Technologies and Therapeutic Use will be of great value to all of those who are actively working in the field of antibodies.
Volume 2: Novel Technologies and Therapeutic Use brings to the forefront current advances in novel technologies for the manufacturing of monoclonal antibodies and also their extensive clinical importance. Following on from Antibodies Volume 1: Production and Purification, this volume concentrates on:
-new technologies in the manufacture of monoclonal antibodies,
-the application of antibodies in cancer therapy and functional genomic therapy,
-the importance of antibodies and prospects of antibody engineering for the future.

This new volume of "Advances in Pharmacology" presents the emerging targets and therapeutics in the treatment of psychostimulant abuse. With a variety of chapters and the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike.
Contributions from the best authors in the fieldAn essential resource for pharmacologists, immunologists, and biochemists

Although the official compendia define a drug substance by its identity, purity, strength, and quality, they normally do not provide other physical or chemical data, nor do they list methods of synthesis or pathways of physical or biological degradation and metabolism. Such information is scattered throughout the scientific literature and the files of pharmaceutical laboratories.
Edited by the Associate Director of Analytical Research and Development for the American Association of Pharmaceutical Scientists, Analytical Profiles of Drug Substances and Excipients brings this information together in one source. The scope of the series has recently been expanded to include profiles of excipient materials.

The field of the excitatory amino acids was born when L-glutamate and L-aspartate were found to be potent convulsants (Hayashi, 1954), and were subsequently found to excite neurons directly (Curtis, Phillis, and Watkins, 1959). Although these studies initiated the hypothesis of glutamate-mediated neurotransmission, it was noted that the ubiquitous actions of glutamate could also reflect a general, nonspecific property of glutamate on neuronal mem branes. It was not until 20 years later that pharmacological, physiological, and biochemical studies provided convincing evidence for a neurotransmitter role for glutamate in the mammalian central nervous system (CNS). With the critical demonstration that the pharmacologically defined glutamate receptors mediate synaptic currents, glutamate rapidly became widely accepted as a majorneurotransmitter by the mid-1980s. This breakthrough, together with the simultaneous findings that glutamate receptors are involved in many essential, as well as pathological, processes in the CNS, instantly transformed the study of glutamate receptors into one of the fastest-growing and most exciting areas of neuroscience. With the cloning of numerous ionotropic glutamate receptor subunits over the last six years, the field has experienced another dramatic acceleration in the understanding of receptor action and in providing the first clear insights into the molecular bases underlying the wealth of pharmacological and physiological data on these receptors."

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABAA receptors underlie classical "phasic" GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.

Phospholipases A2: Brain Phospholipases and their Role in Signal Transduction; A.A. Farooqui, et al. Cell Signaling and Essential Fatty Acids: Reciprocal Regulation of Fatty Acid Release in the Brain by GABA and Glutamate; D.L. Birkle Metabolites of Essential Fatty Acids and Other MembraneDerived Second Messengers in Cell Signaling: A Role for the Arachidonic Acid Cascade in Fast Synaptic Modulation A. Volterra, et al. Dietary Supply of Essential Fatty Acids, Synaptogenesis, and Photoreceptor Biogenesis: Network of Signal Transduction Pathways Involving Lipids; R. Bell et al. Essential Fatty Acids, Excitable Membrane Phospholipids, and Pathophysiology: Conservation of Docosahexaenoic Acid in the Retina; R.E. Anderson, et al. Essential Fatty Acids and Excitable Membrane Phospholipids: Disposition Kinetics of Phospholipid Liposomes; P. Palatini 32 additional articles. Index.

The very latest information on adverse drug effects from the international literature, compiled by an international team of experts.

New reports are presented of adverse drug effects, critically analysed in context, in terms of clinical relevance and importance, and cross-referring to previous reports where necessary. New adverse effects are reported and evaluated, and previously reported adverse effects are re-evaluated in the light of the most recent information.

Unique features:

Reviews in which selected adverse effects are discussed in depth.

Two separate indexes enhance the use of the book, allowing the reader to access information by drug name or by, adverse effects.

Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

From the President of the Research Society on Alcoholism In recent years the alcohol research field has matured and is attracting a substantial number of eager and technically sophisticated researchers. There is a feeling of excitement and premonitions of breakthroughs as more and more of alcohol's actions are being detailed. I, however, have at times been sobered by the perception that the lure of parsimonious explanations and the appeal of studying easily demonstrable effects obscure the critical issues re garding alcohol abuse and alcoholism. Central questions regarding (1) the reinforcing properties of ethanol and other factors responsible for inappro priate consumption of alcohol, (2) the heterogenous characteristics (both bi ologic and sociologic) of the alcoholic population, and (3) the differential predisposition of individuals to alcohol-induced medical problems needed to be vigorously pursued. Researchers who used animals as models for the human condition needed to become more intimately aware of the variety of factors that are of importance in the development of alcoholism in an indi vidual. On the other hand, researchers studying humans needed to attempt to more clearly define and categorize diagnostic criteria and characteristics of various alcoholic populations. Such categorization and continued character ization of alcoholism allows not only for a framework of concepts within which proper animal models for studies of biologic mechanisms can be de veloped but also allows for consideration of the most apt treatment approaches."

This text offers state of the art contributions written by world renown experts which provide an extensive background on specific classes of antibiotics and summarize our understanding as to how these antibiotics might be optimally used in a clinical situation. The book explores pharmacodynamics methods for anti-infective agents, pharmacodynamics of antibacterial agents and non-antibacterial agents, as well as pharmacodynamic considerations and special populations. As part of the Methods in Pharmacology and Toxicology series, chapters include detailed insight and practical information for the lab. Comprehensive and cutting-edge, Antibiotic Pharmacodynamics serves as an ideal reference for scientists investigating advances in antibiotic pharmacodynamics now finding their way into the antibiotic development process used for licensing new antibiotics.