Hypertension has certainly been one of the topics most fre quently discussed at symposia, meetings, and congresses during recent years. There may be several reasons for this; three of them are obvious: firstly, the fact that a large proportion of the world's population is suffering from various forms of hypertensive disease; secondly, increasing knowledge of the pathogenesis of hypertension and of the disturbances underlying it; and, thirdly, the marked progress which has been made in antihypertensive therapy over the past fifteen years. When plans for the present symposium were being drawn up, it was felt that it should not simply bring forth just another meeting on hypertension, but should place particular emphasis on those aspects which had not been adequately discussed at previous symposia of this kind. Curiously enough, the topic which appeared to have received least attention in the past was therapy, although from the practical point of view this is by far the most important. The choice of therapy as the main theme of the whole symposium also seemed to be warranted in view of the relatively long period that had elapsed since effective antihyper tensive treatment became available; the time had in fact come now to pass judgement on the benefits as well as the shortcomings of drug treatment as available today.

This Brief discusses key statistical concepts that facilitate the inferential analysis of data collected from a group of individuals participating in a pharmaceutical clinical trial, the estimation of their clinical significance in the general population of individuals likely to be prescribed the drug if approved, and the related decision-making that occurs at both the public health level (by regulatory agencies when deciding whether or not to approve a new drug for marketing) and the individual patient level (by physicians and their patients when deciding whether or not the patient should be prescribed a drug that is on the market). These concepts include drug safety and efficacy, statistical significance, clinical significance, and benefit-risk balance.

The use of honey can be traced back to the Stone Age. Evidence can be found for its nutritional and medicinal use beginning with prehistoric and ancient civilizations. Currently, there is a resurgence of scientific interest in natural medicinal products, such as honey, by researchers, the medical community, and even the general public. Honey in Traditional and Modern Medicine provides a detailed compendium on the medical uses of honey, presenting its enormous potential and its limitations. The book covers honey's ethnomedicinal uses, chemical composition, and physical properties. It discusses the healing properties of honey, including antimicrobial, anti-inflammatory, and antioxidant properties. It also examines the botanical origin of honey, a critical factor in relation to its medicinal use, along with the complex subject of the varying composition of honey. Honey's antibacterial qualities and other attributes are described in a chapter dedicated to Leptospermum, or Manuka honey, a unique honey with potential for novel therapeutic applications. Chapters explore a variety of medicinal uses for honey, including its healing properties and use in burn and wound management. They review honey's beneficial effects on medical conditions, such as gastrointestinal disorders, cardiovascular diseases, diabetic ulcers, and cancers as well as in pediatrics and animal health and wellness. The book also examines honey-based formulations, modern methods for chemical analysis of honey, and the history and reality of "mad honey." The final chapters cover honey in the food industry, as a nutrient, and for culinary use.

Cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farensyltransferase inhibitors (FTIs); geranylgeranyltransferase inhibitors (GGTIs) are also discussed as potential anticancer drugs. The authors survey in detail such inhibitors as CAAX box peptidomimetics, FPP mimics, and bisubstrate transition state analogs, and critically review their uses in combination with radiation and other cytotoxic agents, such as gemcitabine, cisplatin, and taxanes. Illuminating and richly detailed, Farnesyltransferase Inhibitors in Cancer Therapy constitutes today's standard reference for the pathbreaking use of FTIs and GGTIs in anticancer therapy and offers basic and clinical investigators a comprehensive treatment of the scientific and medical aspects of farnesyltransferase inhibitors.

Macromolecular (specifically peptide-based) drugs could potentially be highly effective medicines. However they have a relatively short duration of action and variable therapeutic index. An example of such a peptide is Glucagon-like Peptide I which could potentially be used as a revolutionary drug for diabetes. This is because it stimulates insulin only when the blood glucose level is high thereby reducing the risk of hypoglycemia (a significant disadvantage of using insulin is that an insulin overdose is the single most potent cause of life-threatening hypoglycemia). However it's short duration of action (half-life of 2 minutes in plasma) precludes its therapeutic use. In this volume, the use of novel therapeutics like GLP1 as an alternative to tradition insulin-based drugs in diabetes is described. Application of Peptide-Based Prodrug Chemistry in Drug Development elucidates the traditional concept of prodrugs as "specialized non-toxic protective groups used in a transient manner to alter or to eliminate certain limiting properties in the parent small molecule" (IUPAC definition). It goes on to provide insight into how prodrugs of peptides (with GLP1 as an example) could be appropriately used to extend the biological half life, broaden the therapeutic index of macromolecules and improve the pharmacodynamics of such drugs. Author explains the logic behind designing peptide prodrugs, synthetic procedures and bioassays to examine the conversion of the prodrug to the drug under therapeutic conditions. The prodrugs described slowly convert to the parent drug at physiological conditions of 37C and pH 7.2 driven by their inherent chemical instability without the need of any enzymatic cleavage. The diketopiperazine and diketomorpholine (DKP and DMP) strategies for prodrug conversion are demonstrated in detail with special emphasis on the chemical flexibility that it offers to develop prodrugs with variable time actions. This book will be of useful to chemists, biochemists, medicinal chemists, biologists and people in the medical profession (doctors). It may be used in undergraduate classes but will certainly help post-graduate students and advanced professionals. The author is grateful to Prof. Richard DiMarchi (Standiford H. Cox Professor of Chemistry and the Linda & Jack Gill Chair in Biomolecular Sciences at Indiana University) for valuable suggestions. The foreword for the book has been written by Prof. Jean Martinez, (Legion d'Honneur awarded by the French Republic; Professor of Chemistry and Medicinal Chemistry of the University of Montpellier, France; and Chairman of European Peptide Society, 2002-2010).

Packed with real-world examples, this book illustrates the 12 principles of green chemistry. These diverse case studies demonstrate to scientists and students that beyond the theory, the challenges of green chemistry in pharmaceutical discovery and development remain an ongoing endeavor. By informing and welcoming additional practitioners to this mission, the negative environmental impact of pharmaceutical products will continue to be minimized. Green chemistry is the methodology by which chemical production in this industry can become more efficient, adding environmental stewardship to the noble mission of treating human disease.

to Cyclic glucans are polysaccharides that are predominantly produced by "Agrobacterium, Bradyrhizobium" and "Rhizobium "sp. and widely used in the pharmaceutical and food industries. In this book, the applications, properties, analytical tools, production and genes of four main cyclic -glucans from microorganisms are highlighted and critically evaluated. As biocompatible and biodegradable renewable resources, they have an immense potential for future applications, which has not yet been fully exploited. This concise review will help to bridge this gap."

Written by internationally acclaimed experts in the economics of innovation, this volume examines how the biotechnology and pharmaceutical sector is affected by the dynamics of innovation, institutions, and public policy. It contributes both theoretically and empirically to the increasingly influential Schumpetarian framework in industrial economics, which places innovation at the centre of the analysis of competition. Both quantitative and qualitative studies are included, and this varied perspective adds to the richness of the volume's insights. The contributors explore different ideas regarding the historical evolution of technology in the sector, and how firms and industry structure have co-evolved with innovation dynamics. Important policy questions are considered regarding the future of innovation in this sector and its impact on the economy.

A comprehensive treatise on the hot working of aluminum and its alloys, Hot Deformation and Processing of Aluminum Alloys details the possible microstructural developments that can occur with hot deformation of various alloys, as well as the kind of mechanical properties that can be anticipated. The authors take great care to explain and differentiate hot working in the context of other elevated temperature phenomena, such as creep, superplasticity, cold working, and annealing. They also pay particular attention to the fundamental mechanisms of aluminum plasticity at hot working temperatures. Using extensive analysis derived from polarized light optical microscopy (POM), transmission electron microscopy (TEM), x-ray diffraction (XRD) scanning electron-microscopy with electron backscatter imaging (SEM-EBSD), and orientation imaging microscopy (OIM), the authors examine those microstructures that evolve in torsion, compression, extrusion, and rolling. Further microstructural analysis leads to detailed explanations of dynamic recovery (DRV), static recovery (SRV), discontinuous dynamic recrystallization (dDRX), discontinuous static recrystallization (dSRX), grain defining dynamic recovery (gDRV) (formerly geometric dynamic recrystallization, or gDRX), and continuous dynamic recrystallization involving both a single phase (cDRX/1-phase) and multiple phases (cDRX/2-phase). A companion to other works that focus on modeling, manufacturing involving plastic and superplastic deformation, and control of texture and phase transformations, this book provides thorough explanations of microstructural development to lay the foundation for further study of the mechanisms of thermomechanical processes and their application.

The second edition of Pharmaceutical Stress Testing: Predicting Drug Degradation provides a practical and scientific guide to designing, executing and interpreting stress testing studies for drug substance and drug product. This is the only guide available to tackle this subject in-depth. The Second Edition expands coverage from chemical stability into the physical aspects of stress testing, and incorporates the concept of Quality by Design into the stress testing construct / framework. It has been revised and expanded to include chapters on large molecules, such as proteins and antibodies, and it outlines the changes in stress testing that have emerged in recent years. Key features include: A renowned Editorial team and contributions from all major drug companies, reflecting a wealth of experience. 10 new chapters, including Stress Testing and its relationship to the assessment of potential genotoxic degradants, combination drug therapies, proteins, oligonucleotides, physical changes and alternative dosage forms such as liposomal formulations Updated methodologies for predicting drug stability and degradation pathways Best practice models to follow An expanded Frequently Asked Questions section This is an essential reference book for Pharmaceutical Scientists and those working in Quality Assurance and Drug Development (analytical sciences, formulations, chemical process, project management).

This is the first book that comprehensively and systematically describes the new technology of hydrophilic interaction liquid chromatography (HILIC). Hydrophilic interaction chromatography is a separation technique suitable for polar and hydrophilic compounds and orthogonal to reversed phase liquid chromatography. From small organic molecules to proteins, the text explores the many applications of HILIC in the analytical field. Winner of the President's Award for Excellence, the author explains how HILIC can significantly improve analytical throughput by shortening sample preparation procedure, which is one of the bottlenecks for drug discovery and development in the pharmaceutical industry.

A major new work on all aspects of water, the most used raw material ingredient in the pharmaceutical and biotechnology industries used as an excipient in pharmaceutical formulations, as a cleaning agent, and as a separately packaged product diluent.

Drawing on the author s extensive field experience with more than 400 pharmaceutical and related water purification systems, the text s numerous case studies illuminate the best and worst of water system design and operation.

The expanded Second Edition also includes new chapters that discuss:

• passivation and electropolishing
• rouging
• ozone systems and accessories
• USP purified water and water for injection
• individual component process and instrumentation diagram (P&IDs) with control interface
• documentation and specification requirements
• systems installation, start-up, and commissioning

Vitamin C may offer significant therapeutic benefits in the treatment of cancer. This book includes chapters by a group of leading scientific researchers documenting the ways cancer can be affected by high doses of ascorbate. After an initial chapter providing a historical perspective, subsequent chapters focus on cancer cell death, reprogramming of somatic cells, recent case studies, and other ways vitamin C can improve outcomes of therapy. Features Includes chapters from a team of leading international scholars Reviews the history of beneficial uses of vitamin C in the treatment of cancer Summarizes recent case studies Discusses how vitamin C may synergistically affect other cancer treatment methods

Vitamin C holds a unique place in scientific and cultural history. In this book, a group of leading scientific researchers describe new insights into the myriad ways vitamin C is employed during normal physiological functioning. In addition, the text provides an extensive overview of the following: the rationale for utilizing vitamin C in the clinic, updates on recent uses of vitamin C in cancer treatment through high-dose intravenous therapies, the role vitamin C plays in the treatment of sepsis and infectious disease, management of the ways vitamin C can improve stem cell differentiation, as well as vitamin C use in other important health situations. Features Includes chapters from a team of leading international scholars Reviews the history and recent research on the functions, benefits, and uses of vitamin C Focuses special attention on the way vitamin C can be used in the treatment of cancers Discusses how vitamin C can be employed against infectious disease

Colloidal drug delivery systems present a range of therapeutic benefits in the treatment of a number of challenging conditions, allowing researchers to cross barriers that have previously prevented efficient treatment while offering improved and more targeted absorption. Summarizing recent research in the field, Colloids in Drug Delivery assembles the work of 65 of the world's leading colloid scientists who examine the full spectrum of this rapidly emerging science, from pure to applied, most of it drawn from their own experience and research. The book begins by examining the basics of surfactant and polymer surface activity and self-assembly, the various types of structures formed by such compounds, and their use in drug delivery and biotechnology. It examines the development of controlled and targeted delivery systems by utilizing the various properties of colloids before moving on to discuss various applications and fields of research. Topics discussed include: The use of hard, soft, and macromolecular colloidal drug delivery systems formed by surfactants, polymers, proteins, and lipids Recent advances in procolloidal systems, self-emulsifying drug delivery systems, and aerosol applications to pharmaceutical drug delivery Colloidal nanocarriers for imaging applications and the treatment of dental and periodontal diseases Classification and application of colloidal drug delivery systems in tumor targeting The use of colloids for improved nasal, ocular, vaginal, oral, buccal, gastrointestinal, and colon drug delivery Examining topics necessary to the critical evaluation of a drug candidate's potential for delivery, the book also describes the preparation, classification, interfacial activity, surface modifications and influence on particle characteristics, drug delivery, and drug targeting. Each chapter in this expansive volume explains why a particular system is used for the intended application, how it is made, and how it behaves. All those concerned with the research, development, and manufacture of drugs will find this a valuable reference, offering a wealth of research upon which they can build.

Useful Statistical Approaches for Addressing Multiplicity Issues Includes practical examples from recent trials Bringing together leading statisticians, scientists, and clinicians from the pharmaceutical industry, academia, and regulatory agencies, Multiple Testing Problems in Pharmaceutical Statistics explores the rapidly growing area of multiple comparison research with an emphasis on pharmaceutical applications. In each chapter, the expert contributors describe important multiplicity problems encountered in pre-clinical and clinical trial settings. The book begins with a broad introduction from a regulatory perspective to different types of multiplicity problems that commonly arise in confirmatory controlled clinical trials, before giving an overview of the concepts, principles, and procedures of multiple testing. It then presents statistical methods for analyzing clinical dose response studies that compare several dose levels with a control as well as statistical methods for analyzing multiple endpoints in clinical trials. After covering gatekeeping procedures for testing hierarchically ordered hypotheses, the book discusses statistical approaches for the design and analysis of adaptive designs and related confirmatory hypothesis testing problems. The final chapter focuses on the design of pharmacogenomic studies based on established statistical principles. It also describes the analysis of data collected in these studies, taking into account the numerous multiplicity issues that occur. This volume explains how to solve critical issues in multiple testing encountered in pre-clinical and clinical trial applications. It presents the necessary statistical methodology, along with examples and software code to show how to use the methods in practice.

All too often, the words "computer validation" strike terror into the hearts of those new to the process and may even cause those familiar with it to tremble. Validating Pharmaceutical Systems: Good Computer Practice in Life Science Manufacturing delineates GCP, GLP, and GMP regulatory requirements and provides guidance from seasoned practitioners on how to fulfill them. John Andrews and his team tackle the perceived complexities surrounding the validation of a wide variety of automated systems. Sprinkled with case studies and real-life examples, the book offers a step-by-step review of topics such as planning, design, auditing, risk management, and specification. The in-depth, by example coverage demystifies the challenges of manufacturing execution systems(MES), laboratory information management systems(LIMS), and network qualification. The first section examines the different levels of automated systems used throughout the drug development, manufacture, and delivery lifecycle, using the GAMP 4 lifecycle approach to their validation. The second section uncovers some real-life applications of GAMP 4 to different areas of the regulations such as GLP, GCP, GMP, and GDP. The book explores some of the latest thinking on computer validation and reflects changes that have occurred in the industry since the early days of validation. The contributors are a deliberate blend of those who have faced the problems of the 1990s and the Y2K controversies and those who have more recently arrived on the scene and made an impact on the perception of validation of automated systems across the field of GxP. They do more than show you how to do the right thing; they show you how to do the right thing in compliance with regulations.

Adaptive clinical trial designs, unlike traditional fixed clinical trial designs, enable modification of studies in response to the data generated in the course of the trial. This often results in studies that are substantially faster, more efficient, and more powerful. Recent developments in web-based real-time data entry and advances in statistical methods have made adaptive clinical trials much more popular because they have become both more practical and attractive. However, there is paucity of resources that explain the mathematical framework and the practical considerations for adaptive designs without the use of highly technical statistical jargon. Suitable for readers in academia, industry, and government involved in drug development, Adaptive and Flexible Clinical Trials is the first book that comprehensively explains all essential aspects of adaptive clinical trials. Written in an easy-to-understand style aimed at clinicians and other non-statisticians, this book focuses not on the statistical details, but rather on the application of statistical concepts for adaptive clinical trials. Utilizing concrete examples, the book thoroughly explains the design, conduct, and analysis of adaptive and flexible clinical trials, allowing readers to select and design the appropriate trial designs from a conceptual perspective. From basic theory to real-life practical issues, it covers all aspects of adaptive and flexible clinical trials, including regulatory issues, interim analysis, adaptive dosing, and sequential designs.

When a pharmaceutical company decides to build a Quality System, it has to face the fact that there aren't any guideline that define exactly how such a system has to be built. With terms such as quality system, quality assurance, and quality management used interchangeably, even defining the system's objectives is a problem. This book provides a practical guide to building a quality system. Beginning with explanations of key terms and concepts, it covers ISO 9000 and GMP and how to combine them, and includes a matrix showing their similarities and differences. Implementation reviews illustrate how Quality (Management) Systems have been installed successfully in pharmaceutical companies. Also covered are the individual components of a Quality System; auditing, validation, and supplier qualification systems; and Hazard Analysis Critical Control Points (HACCP).

Adaptive Designs for Sequential Treatment Allocation presents a rigorous theoretical treatment of the results and mathematical foundation of adaptive design theory. The book focuses on designing sequential randomized experiments to compare two or more treatments incorporating information accrued along the way. The authors first introduce the terminology and statistical models most commonly used in comparative experiments. They then illustrate biased coin and urn designs that only take into account past treatment allocations as well as designs that use past data, such as sequential maximum likelihood and various types of doubly adaptive designs. The book also covers multipurpose adaptive experiments involving utilitarian choices and ethical issues. It ends with adaptive methods that include covariates in the design. The appendices present basic tools of optimal design theory and address Bayesian adaptive designs. This book helps readers fully understand the theoretical properties behind various adaptive designs. Readers are then equipped to choose the best design for their experiment.

The development of suitable assays, the integration of appropriate technology, and the effective management of the essential infrastructure are all critical to the success of any high-throughput screening (HTS) endeavor. However, few scientists have the multidisciplinary experience needed to control all aspects of an HTS drug discovery project. A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery integrates the experience of diverse experts who offer fundamental and practical guidance across numerous situations. The book first discusses assay developments for important target classes such as protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and heat shock proteins. It next examines assay developments for cell viability, apoptosis, and infectious diseases. The contributors explore the application of emerging technologies and systems, including image-based high content screening, RNA interference, and primary cells. Finally, they discuss the essential components of the integrated HTS process, such as screening automation, compound library management, the screening of natural products from botanical sources, and screening informatics. Designed to motivate researchers to bring further advances to the field, this volume provides practical guidance on how to initiate, validate, optimize, and manage a bioassay intended to screen large collections of compounds. Drawing on the knowledge from experts actively involved in assay development and HTS, this is a resource that is both comprehensive and focused.

A must-have reference for any researcher or scientist interested in cutaneous protective mechanisms, this guide provides expertly researched chapters on every aspect of stratum corneum structure, function, and development, as well as detailed sections on barrier-repair strategies and the role of barrier function in diseases such as atopic dermatitis, psoriasis, and ichthyosis.

Since the advent of cDNA microarrays, oligonucleotide array technology, and gene chip analysis, genomics has revolutionized the entire field of biomedical research. A byproduct of this revolution, toxicogenomics is a fast-rising star within toxicological analysis. Gathering together leading authors and scientists at the forefront of the field, An Introduction to Toxicogenomics provides a comprehensive overview of this new discipline. With a focus on toxicology, it introduces the basic principles of microarray/oligonucleotide array-based genomic analysis and explains how it fits into the field of biomedical research. These discussions provide an overview to the actual mechanics of the analyses themselves and offer insights on handling and quality control. Then the book features an important section on the basics of data analysis and clustering methods such as genetic algorithms. Finally, it covers the application of expression profiling in the field of toxicology and addresses the two fundamental types of analysis in detail, with sections dedicated to both mechanistic and predictive studies. Although toxicogenomics promises fast, efficient techniques and information-rich data, much of its potential remains untapped. An Introduction to Toxicogenomics consolidates the concepts underlying the field to provide a solid foundation from which to begin your research endeavors.

Written especially for the pharmaceutical industry professional, this book addresses each part of the life-cycle of engineering change control. It covers issues in the EU and US and describes the operational requirements and responsibilities that ensure change controls are effectively applied and recorded. Providing guidance on how to demonstrate that a change control system is working, the book includes chapters on computer validation, customization of the change process to each project's needs, and case histories and anecdotes illustrate key points and provide a basis for change control training. It gives readers a toolbox for ensuring that adequate controls are implemented.

Since the publication of the first edition of Pharmaceutical Biotechnology over a decade ago, a not-so-subtle shift in the meaning of the term "biotechnology" has occurred. It has come to mean something very specific, namely the development of drug substances with large protein and polypeptide molecules. These substances can be used as drugs in their own right but may also be used to manipulate cellular DNA in order to produce a required molecule that is believed to have desirable properties in the treatment of a disease. Accordingly, the second edition of this popular text reflects that change of definition by including new material that explores the development of these protein-based therapeutic substances. See what's new in the Second Edition: Expanded coverage of the formulation of proteins Additional information on proteins used as drug delivery systems Detailed discussion of interactions between proteins and phospholipids Increased information on proteomics and gene therapy Exploration of pulmonary administration and oral delivery of proteins A broad review of vaccines Discussion of genetic engineering and genomics Challenges and issues involved in the development and the production of a drug