Heparins remain amongst the most commonly used drugs in clinical practice. Almost 100 years have passed since the initial discovery of this complex substance and, during this time, understanding of the nature and uses of heparin and related molecules has grown dramatically. The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources.

ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian

Introduction to Fragment-Based Drug Discovery, by Daniel A. Erlanson

Fragment Screening Using X-Ray Crystallography, by Thomas G. Davies and Ian J. Tickle

Hsp90 Inhibitors and Drugs from Fragment and Virtual Screening, by Stephen Roughley, Lisa Wright, Paul Brough, Andrew Massey and Roderick E. Hubbard

Combining NMR and X-ray Crystallography in Fragment-Based Drug Discovery: Discovery of Highly Potent and Selective BACE-1 Inhibitors, by Daniel F. Wyss, Yu-Sen Wang, Hugh L. Eaton, Corey Strickland, Johannes H. Voigt, Zhaoning Zhu and Andrew W. Stamford

Combining Biophysical Screening and X-Ray Crystallography for Fragment-Based Drug Discovery, by Michael Hennig, Armin Ruf and Walter Huber

Targeting Protein Protein Interactions and Fragment-Based Drug Discovery, by Eugene Valkov, Tim Sharpe, May Marsh, Sandra Greive and Marko Hyvonen

Fragment Screening and HIV Therapeutics, by Joseph D. Bauman, Disha Patel and Eddy Arnold

Fragment-Based Approaches and Computer-Aided Drug Discovery, by Didier Rognan"

Examining the implications and practical implementation of multi-disciplinary International Conference on Harmonization (ICH) topics, this book gives an integrated view of how the guidelines inform drug development strategic planning and decision-making. Addresses a consistent need for interpretation, training, and implementation examples of ICH guidelines via case studies Offers a primary reference point for practitioners addressing the dual challenge of interpretation and practical implementation of ICH guidelines Uses case studies to help readers understand and apply ICH guidelines Provides valuable insights into guidelines development, with chapters by authors involved in generating or with experience implementing the guidelines Includes coverage of stability testing, analytical method validation, impurities, biotechnology drugs and products, and good manufacturing practice (GMP)

Long acting veterinary formulations play a significant role in animal health, production and reproduction within the animal health industry. Such technologies offer beneficial advantages to the veterinarian, farmer and pet owner. These advantages have resulted in them growing in popularity in recent years. The pharmaceutical scientist is faced with many challenges when innovating new products in this demanding field of controlled release. This book provides the reader with a comprehensive guide on the theories, applications, and challenges associated with the design and development of long acting veterinary formulations. The authoritative chapters of the book are written by some of the leading experts in the field. The book covers a wide scope of areas including the market influences, preformulation, biopharmaceutics, in vitro drug release testing and specification setting to name but a few. It also provides a detailed overview of the major technological advances made in this area. As a result this book covers everything a formulation scientist in industry or academia, or a student needs to know about this unique drug delivery field to advance health, production and reproduction treatment options and benefits for animals worldwide.

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

Central Nervous System disorders have an enormous impact on individuals and on society as a whole. The development of better treatments is crucial and is a major focus of pharmaceutical and biotechnology companies. This book explains the complicated process of CNS drug development in a way that is engaging for any interested professional or student. Chapters cover each stage of drug development, from pre-clinical research through all phases of clinical trials, to reporting to the regulatory authorities. Other key issues covered include strategic considerations, regulatory constraints, dissemination of results and ethical considerations. The user-friendly format and style enable readers to find important information quickly and easily. Written and edited by experts from different sectors actively engaged in CNS drug development, this is a unique resource for drug developers, investigators, academics and clinicians.

Controlled Release in Oral Drug Delivery provides focus on specific topics, complementing other books in the initial CRS series. Each chapter sets the context for the inventions described and describe the latitude that the inventions allow. In order to provide some similar look to each chapter, the coverage includes the historical overview, candidate drugs, factors influencing design and development, formulation and manufacturing and delivery system design. This volume was written along three main sections: the relevant anatomy and physiology, a discussion on candidates for oral drug delivery and the major three groups of controlled release systems: diffusion control (swelling and inert matrices); environmental control (pH sensitive coatings, time control, enzymatic control, pressure control) and finally lipidic systems.

Finally - a book that covers all aspects of the illicit use of cocaine, amphetamines, ecstasy and/or designer drugs such as GHB, written by two experts in their field. The use of these drugs remains a continuous threat in health and medical care delivery, and this book will be an essential asset to the physician who may have to face the evaluation of patients whose use of these drugs compromises an effective treatment plan for other health issues. The book has been conceived to fill the void in existing physician reference materials, and provides a comprehensive review of the theoretical knowledge and scope of pharmacotherapy in individuals who are hooked on a psychoactive substance. While detailed scientific information is obtainable in other major articles, the book's straightforward format and style, along with its illustrations, will make for easy reading as emphasis is put on information specifically related to drugs that occur most abused in today's society. The information provided is based on clinical practice rather than pure experimental data, which will give the physician more effective tools useful in their daily practice. Many mechanisms of action of abuse are described in detail and references are provided to direct the reader to further sources for additional information. As a special feature, the book incorporates uncluttered tables and charts, which result in immediate clarification of the mode of action on the central nervous system and the reason for misuse, thus avoiding usual long and fatiguing text in common reference books. The book aims to give the reader a clear and concise plan on what to do when being faced with an overdose situation. A well-organized Table of Contents rapidly leads the reader from general pharmacological issues to the specific overdose syndrome and its management. Additionally, significant emphasis is placed on the practical do's and don'ts for physicians, with special reference to the predictive signs of aberrant drug-related behavior and the identification of the drug diverter by using urine drug screening.

Biologics have revolutionised the treatment of many severe conditions, delivering exceptional clinical results but also producing exceptionally high prices. As patents expire, copies and price competition are expected throughout the world. However, due to the intrinsic heterogeneity and molecular complexity of biologic medicinal products, their copies cannot simply be authorized under the "generic rule" valid for small chemical entities. In response, a dedicated regulation was issued in the European Union. It is based on the concept of "biological medicinal products similar to a biological reference product", or "biosimilars". This book analyses the context of biotechnological production and addresses the European legal framework for biosimilar market approval. It highlights post-market authorisation issues, such as Risk Management Plans and substitution of products, and outlines some other issues, such as cost management and international nomenclature. This book is primarily intended for hospital-based physicians and pharmacists. It will also be a valuable resource for all actors from all countries who want to better understand the emergence of these new medicinal products within the European context.

Pharmacy Practice discusses the many factors impinging on daily practice and the place of pharmacy in the delivery of health care. The book goes beyond simply considering how pharmacy is practised and draws on a diverse range of disciplines, including sociology, social policy, psychology, anthropology, history and health economics, with each contributor bringing a unique perspective and insight into that practice. In this fully updated edition, the content and presentation have been thoroughly revised and new material added to reflect the many changes that have occurred in the last edition, particularly in pharmacy and health policy and professional regulation and development. The book provides the background and context for issues currently impacting professional practice and which will determine how pharmacy will develop in the future.

Discussing existing techniques, ongoing research, new approaches, and basic concepts in the treatment of nail diseases, Topical Nail Products and Ungual Drug Delivery summarizes the current knowledge and represents a jumping-off point for creating novel techniques of drug delivery across the nail. A growing area of pharmaceutical research, the search for efficient delivery techniques that can cross the nail barrier has yielded several effective strategies, brought together in this book. Topics Include Nail anatomy, physiology, diseases, and treatment Permeability of the nail plate Topical nail formulations Approaches to enhance ungual and trans-ungual drug delivery In vitro and in vivo models to evaluate topical nail formulations Nail sampling techniques Bioengineering of the nail Trans-ungual iontophoresis Pharmacokinetics of drugs in the nail apparatus Onychopharmacokinetics: proposed model insight Photodynamic therapy of nail diseases The nail as a surrogate for investigating drug use

The field of molecular medicine covers the medical interventions targeting molecular structures and mechanisms that are involved in disease progression. In cancer, several molecular mechanisms have been shown to impact its progression, aggressiveness and chemoresistance. Increasing evidence demonstrates the role of nanotechnology and outcome of molecular therapy. Several books have discussed molecular biology and mechanisms involved in cancer, but this text gives an account of molecular therapeutics in cancer relating to advancements of nanotechnology. It provides a description of the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology. Key Features: Provides current information in the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology Presents important aspects of nanotechnology in the site-specific delivery of anticancer agents Includes up to date information on oligonucleotide and gene based therapies in cancer Describes small targeted molecules, antibodies and oligonucleotides which have shown to selectively target the molecular structures thereby influencing signal transduction Facilitates discussion between researchers involved in cancer therapy and nanoscientists

The aim and scope of this book is to highlight the sources, isolation, characterization and applications of bioactive compounds from the marine environment and to discuss how marine bioactive compounds represent a major market application in food and other industries. It discusses sustainable marine resources of macroalgal origin and gives examples of bioactive compounds isolated from these and other resources, including marine by-product and fisheries waste streams. In addition, it looks at the importance of correct taxonomic characterization."

Summary: The focus of this book is on how the U.S. FDA will approve biosimilar drugs, as learned from recent approvals by the FDA. Understanding the limitations of the statutory limits and non-inferiority testing are presented as tools to obviate patient trials and minimize testing of immunogenicity. An in-depth scientific, mathematical and statistical view of the tools required to establish biosimilarity of biological drugs of different complexity -- a must for every developer of biosimilars. Features: First comprehensive analysis based on new guidelines and approval packages of several biosimilars Presents the first approach to challenge FDA in reducing or eliminating any testing in patients. Provides a comprehensive understanding of the U.S. statutory requirements vis-a-vis the regulatory guidelines Provides model CQA and Analytical Similarity testing protocols for cytokines and monoclonal antibodies Allow creation of a fast-to-market pathway to develop biosimilars

Monoclonal antibodies (MAbs) are currently the major class of protein bio therapeutic being developed by biotechnology and pharmaceutical companies. Monoclonal Antibodies discusses the challenges and issues revolving around development of a monoclonal antibody produced by recombinant DNA technology into a therapeutic agent.This book covers downstream processing which includes design of processes to manufacture the formulation, formulation design, fill and finish into closure systems and routes of administration. The characterization of the final drug product is covered where the use of biophysical methods combined with genetic engineering is used to understand the solution properties of the formulation. The latter has become very important since many indications such as arthritis and asthma require the development of formulations for subcutaneous delivery (SC). The development of formulations for IV delivery is also important and comes with a different set of challenges. The challenges and strategies that can overcome these limitations are discussed in this book, starting with an introduction to these issues, followed by chapters detailing strategies to deal with them. Subsequent chapters explore the processing and storage of mAbs, development of delivery device technologies and conclude with a chapter on the future of mAbs in therapeutic remedies.

Clinical pharmacology plays an important role in today's medicine. Due to the high sensitivity, selectivity, and affordability of a mass spectrometer (MS), the high performance liquid chromatography - mass spectrometry (LC-MS) analytical technique is widely used in the determination of drugs in human biological matrixes for clinical pharmacology. Specifically, LC-MS is used to analyze: anticancer drugs antidementia drugs antidepressant drugs antiepileptic drugs antifundal drug antimicrobial drugs antipsychotic drugs antiretroviral drugs anxiolytic/hypnotic drugs cardiac drugs drugs for addiction immunosuppressant drugs mood stabilizer drugs This book will primarily cover the various methods of validation for LC-MS techniques and applications used in modern clinical pharmacology.

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

Long acting injections and implants improve therapy, enhance patient compliance, improve dosing convenience, and are the most appropriate formulation choice for drugs that undergo extensive first pass metabolism or that exhibit poor oral bioavailability. An intriguing variety of technologies have been developed to provide long acting injections and implants. Many considerations need to go into the design of these systems in order to translate a concept from the lab bench to actual therapy for a patient. This book surveys and summarizes the field.

Topics covered in "Long Acting Injections and Implants" include the historical development of the field, drugs, diseases and clinical applications for long acting injections and implants, anatomy and physiology for these systems, specific injectable technologies (including lipophilic solutions, aqueous suspensions, microspheres, liposomes, in situ forming depots and self-assembling lipid formulations), specific implantable technologies (including osmotic implants, drug eluting stents and microfabricated systems), peptide, protein and vaccine delivery, sterilization, drug release testing and regulatory aspects of long acting injections and implants.

This volume provides essential information for experienced development professionals but was also written to be useful for scientists just beginning work in the field and for others who need an understanding of long acting injections and implants. This book will also be ideal as a graduate textbook."

Alzheimer's Disease is a progressive neurodegenerative disorder of late life with devastating consequences for the afflicted and their carers and poses one of the major challenges to medical research. Until recently, little hope of effective therapies capable of slowing the disease process or preventing its occurrence was apparent. With recent advances in the genetics and molecular biology of the disease processes and the demonstration of the involvement of multiple aetiological factors, however, real chances are now appearing for the identification of preventive drugs. In this discussion, experts from disciplines ranging from molecular genetics to the clinic provide review and novel data concerning the aetiology of AD and the establishment of drugfinding screening methods.

Only four short decades ago, the control of insect pests by means of chemicals was in its early infancy. The pioneers in the area consisted largely of a group of dedicated applied entomologists working to the best of their abilities with a very limited arsenal of chemicals that included inorganics (arsenicals, fluorides, etc.), some botanicals (nicotine), and a few synthetic organics (dinitro-o-cresol, organothiocyanates). Much of the early research was devoted to solving practical problems associated with the formulation and application of the few existing materials, and although the discovery of new types of insecticidal chemicals was undoubtedly a pipe dream in the minds of some, little or no basic research effort was expended in this direction. The discovery of the insecticidal properties of DDT by Paul Miiller in 1939 has to be viewed as the event which marked the birth of modern insecticide chemistry and which has served as the cornerstone for its subse quent developement. DDT clearly demonstrated for the first time the dramatic potential of synthetic organic chemicals for insect control and provided the initial stimulus which has caused insecticide chemistry to become a field not only of immense agricultural and public health importance but also one that has had remarkable and unforseeable repercussions in broad areas of the physical, biological, and social sciences. Indeed, there can be few other synthetic chemicals which will be judged in history to have had such a broad and telling impact on mankind as has DDT."

This volume is intended to provide the reader with a breadth of understanding regarding the many challenges faced with the formulation of poorly water-soluble drugs as well as in-depth knowledge in the critical areas of development with these compounds. Further, this book is designed to provide practical guidance for overcoming formulation challenges toward the end goal of improving drug therapies with poorly water-soluble drugs. Enhancing solubility via formulation intervention is a unique opportunity in which formulation scientists can enable drug therapies by creating viable medicines from seemingly undeliverable molecules. With the ever increasing number of poorly water-soluble compounds entering development, the role of the formulation scientist is growing in importance. Also, knowledge of the advanced analytical, formulation, and process technologies as well as specific regulatory considerations related to the formulation of these compounds is increasing in value. Ideally, this book will serve as a useful tool in the education of current and future generations of scientists, and in this context contribute toward providing patients with new and better medicines.

This book presents the laboratory, scientific and clinical aspects of nanomaterials used for medical applications in the fields of regenerative medicine, dentistry and pharmacy. It gives a broad overview on the in vitro compatibility assessment of nanostructured materials implemented in the medical field by the combination of classical biological protocols and advanced non-destructive nano-precision techniques with special emphasis on the topographical, surface energy, optical and electrical properties. Materials in the physical form of nanoparticles, nanotubes, and thin films are addressed in terms of their toxicity. The different pillars of the Nanomedicine field are also highlighted. The book takes an interdisciplinary approach of medicine, biology, pharmacy, physics, chemistry, engineering, nanotechnology and materials science. The international group of authors specifically chosen for their distinguished expertise belong to the academic and industrial world in order to provide a broader perspective. It appeals to researchers and graduate students.