The first chapter describes the oldest method of communication between living systems in Nature, the chemical language. Plants, due to their lack of mobility, have developed the most sophisticated way of chemical communication. Despite that many examples involve this chemical communication process - allelopathy, there is still a lack of information about specific allelochemicals released into the environment, their purpose, as well as in-depth studies on the chemistry underground. These findings are critical to gain a better understanding of the role of these compounds and open up a wide range of possibilities and applications, especially in agriculture and phytomedicine. The most relevant aspects regarding the chemical language of plants, namely, kind of allelochemicals have been investigated, as well as their releasing mechanisms and their purpose, are described in this chapter. The second chapter is focused on the natural products obtained from Hypericum L., a genus of the family Hypericaceae within the dicotyledones. Hypericum has been valued for its important biological and chemical properties and its use in the treatment of depression and as an antibacterial has been well documented in primary literature and ethnobotanical reports. The present contribution gives a comprehensive summary of the chemical constituents and biological effects of this genus. A comprehensive account of the chemical constituents including phloroglucinol derivatives, xanthones, dianthrones, and flavonoids is included. These compounds show a diverse range of biological activities that include antimicrobial, cytotoxic, antidepressant-like, and antinociceptive effects. The third chapter addresses microtubule stabilizers, which are a mainstay in the treatment of many solid cancers and are often used in combination with molecularly targeted anticancer agents and immunotherapeutics. The taccalonolides are a unique class of such microtubule stabilizers isolated from plants of Tacca species that circumvent clinically relevant mechanisms of drug resistance. Although initial reports suggested that the microtubule stabilizing activity of the taccalonolides is independent of direct tubulin binding, additional studies have found that potent C-22,23 epoxidated taccalonolides covalently bind the Aspartate 226 residue of -tubulin and that this interaction is critical for their microtubule stabilizing activity. Some taccalonolides have demonstrated in vivo antitumor efficacy in drug-resistant tumor models with exquisite potency and long-lasting antitumor efficacy as a result of their irreversible target engagement. The recent identification of a site on the taccalonolide scaffold that is amenable to modification has provided evidence of the specificity of the taccalonolide-tubulin interaction and the opportunity to further optimize the targeted delivery of the taccalonolides to further improve their anticancer efficacy and potential for clinical development.

Early anthropological evidence for plant use as medicine is 60,000 years old as reported from the Neanderthal grave in Iraq. The importance of plants as medicine is further supported by archeological evidence from Asia and the Middle East. Today, around 1.4 billion people in South Asia alone have no access to modern health care, and rely instead on traditional medicine to alleviate various symptoms. On a global basis, approximately 50 to 80 thousand plant species are used either natively or as pharmaceutical derivatives for life-threatening conditions that include diabetes, hypertension and cancers. As the demand for plant-based medicine rises, there is an unmet need to investigate the quality, safety and efficacy of these herbals by the "scientific methods". Current research on drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, analytical, and molecular techniques. For instance, high throughput robotic screens have been developed by industry; it is now possible to carry out 50,000 tests per day in the search for compounds, which act on a key enzyme or a subset of receptors. This and other bioassays thus offer hope that one may eventually identify compounds for treating a variety of diseases or conditions. However, drug development from natural products is not without its problems. Frequent challenges encountered include the procurement of raw materials, the selection and implementation of appropriate high-throughput bioassays, and the scaling-up of preparative procedures. Research scientists should therefore arm themselves with the right tools and knowledge in order to harness the vast potentials of plant-based therapeutics. The main objective of Plant and Human Health is to serve as a comprehensive guide for this endeavor. Volume 1 highlights how humans from specific areas or cultures use indigenous plants. Despite technological developments, herbal drugs still occupy a preferential place in a majority of the population in the third world and have slowly taken roots as alternative medicine in the West. The integration of modern science with traditional uses of herbal drugs is important for our understanding of this ethnobotanical relationship. Volume 2 deals with the phytochemical and molecular characterization of herbal medicine. Specifically, it focuess on the secondary metabolic compounds, which afford protection against diseases. Lastly, Volume 3 discusses the physiological mechanisms by which the active ingredients of medicinal plants serve to improve human health. Together this three-volume collection intends to bridge the gap for herbalists, traditional and modern medical practitioners, and students and researchers in botany and horticulture.

Absorption, Distribution, Metabolism and Excretion (ADME) processes and their relationship with the design of dosage forms and the success of pharmacotherapy form the basis of this upper level undergraduate/graduate textbook. As an introduction oriented to pharmacy students, it is also written for scientist from different fields outside of pharmaceutics. (e.g. material scientist, material engineers, medicinal chemists) who might be working in a positions in pharmaceutical companies or whose work might benefit from basic training in the ADME concepts and some biological background. Pedagogical features such as objectives, keywords, discussion questions, summaries and case studies add valuable teaching tools. This book will provide not only general knowledge on ADME processes but also an updated insight on some hot topics such as drug transporters, multi-drug resistance related to pharmacokinetic phenomena, last generation pharmaceutical carriers (nanopharmaceuticals), in vitro and in vivo bioequivalence studies, biopharmaceuticals, pharmacogenomics, drug-drug and food-drug interactions, and in silico and in vitro prediction of ADME properties. In comparison with other similar textbooks, around half of the volume would be focused on the relationship between expanding scientific fields and ADME processes. Each of these burgeoning fields has a separate chapter in the second part of the volume, and was written with leading experts on the correspondent topic, including scientists and academics from USA and UK (Duquesne University School of Pharmacy, Indiana University School of Medicine, University of Utah College of Pharmacy, University of Maryland, University of Bath). Additionally, each of the initial chapters dealing with the generalities of drug absorption, distribution, metabolism and excretion would include relevant, classic examples related to each topic with appropriate illustrations (e.g. importance of active absorption of levodopa, implications in levodopa administration, drug drug interactions and food drug interactions emerging from the active uptake; intoxication with paracetamol as a result of glutathione depletion, CYP induction and its relationship with acute liver failure caused by paracetamol, etc). ADME Processes and Pharmaceutical Sciences is written as a core textbook for ADME processes, pharmacy, pharmacokinetics, drug delivery, biopharmaceutics, drug disposition, drug design and medicinal chemistry courses.

Intelligent Nanomaterials for Drug Delivery Applications discusses intelligent nanomaterials with a particular focus on commercial and premarket tools. The book looks at the applications of intelligent nanomaterials within the field of medicine and discusses their future role. This includes the use of intelligent nanomaterials for drugs used in cardiovascular and cancer treatments and examines the promising market of nanoparticles for biomedical and biosensing applications. This resource will be of great interest to scientists and researchers involved in multiple disciplines, including micro- and nano-engineering, bionanotechnology, biomedical engineering, and nanomedicine, as well as pharmaceutical and biomedical industries.

This third edition volume expands on the previous editions with new topics that cover drug discovery through translational bioinformatics, informatics, clinical research informatics, as well as clinical informatics. The chapters discuss new methods to study target identification, genome analysis, cheminformatics, protein analysis, and text mining. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials, software workflows, reagents and on-line resources, together with step-by-step, readily reproducible laboratory and computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Bioinformatics and Drug Discovery, Third Edition is a valuable resource for anyone interested in drug design, including academicians (biologists, informaticists and data scientists, chemists, and biochemists), clinicians, and pharmaceutical scientists.

Dendrimers are repeatedly branched and roughly spherical large molecules. They can be used in various medical applications, such as anticancer polymeric nanomedicines and nanocarriers, gene carriers and vectors in gene delivery, contrast agents for molecular imaging and vaccines against infectious diseases and cancer. The highly branched, multivalent nature and molecular architecture of dendrimers make them ideal tools for a variety of tissue engineering applications. This book describes different categories of dendrimers, their biomedical and physico-chemical applications as well as convergent and divergent syntheses, click chemistry and ligation strategies. It is a rich source of information for researchers in biochemistry and pharmacology working on drug development as well as for organic chemists who are engaged in synthesis of dendrimers.

This book is the second of two volumes that offer a comprehensive, up-to-date account of current knowledge regarding high-density lipoprotein (HDL), the changes that occur in HDL under different conditions, the clinical applications of HDL, and means of enhancing HDL functionality. In this volume, the focus is on the improvement of HDL, enhancement of its functionality, and the use of HDL for therapeutic purposes. In the first section, up-to-date information is provided on such topics as the tumor regression-promoting and antidiabetic activities of reconstituted HDL containing V156K apolipoprotein A-I, the enhancement of HDL effects by high doses of vitamin C, the benefits derived from incorporation of growth hormones 1 and 2 into rHDL, and the biological functions of omega-3 linolenic acid in rHDL. The enhancement of HDL functionality by policosanol and the resultant benefits are thoroughly examined in a separate section. Readers will also find the latest information on clinical applications of HDL. Here, specific topics include the enhancement of adenoviral gene delivery and the delivery of rapamycin. In documenting the latest knowledge in this field, this volume will be of interest to both researchers and clinicians.

Computational biology drives discovery through its use of high-throughput informatics approaches. This book provides a road map of the current drug development process and how computational biology approaches play a critical role across the entire drug discovery pipeline. Through the use of previously unpublished, real-life case studies the impact of a range of computational approaches are discussed at various phases of the pipeline. Additionally, a focus section provides innovative visualisation approaches, from both the drug discovery process as well as from other fields that utilise large datasets, recognising the increasing use of such technology. Serving the needs of early career and more experienced scientists, this up-to-date reference provides an essential introduction to the process and background of drug discovery, highlighting how computational researchers can contribute to that pipeline.

This second edition of Clinical Use of Anti-Infective Agents provides a comprehensive overview of current approaches to using drugs to treat infections, including historical perspectives, definitions, and discussion of pharmacokinetics and pharmacodynamics and their uses. It includes a detailed explanation of different classes of drugs, outlining their spectrum, pharmacokinetics, side effects, and dosing in clinical settings. This book has been designed as a reference tool for pharmacists, clinicians, nurse practitioners, and clinical microbiologists, as well as a teaching vehicle for students studying infection and patient treatment. Each section includes references allowing for in-depth study of specific agents, Q&As, and illustrative case studies accompanied by commentary on how to approach patients and organisms, optimal methods of making a diagnosis, and prescribing treatment.

From its origins as a niche technique more than 15 years ago, fragment-based approaches have become a major tool for drug and ligand discovery, often yielding results where other methods have failed. Written by the pioneers in the field, this book provides a comprehensive overview of current methods and applications of fragment-based discovery, as well as an outlook on where the field is headed. The first part discusses basic considerations of when to use fragment-based methods, how to select targets, and how to build libraries in the chemical fragment space. The second part describes established, novel and emerging methods for fragment screening, including empirical as well as computational approaches. Special cases of fragment-based screening, e. g. for complex target systems and for covalent inhibitors are also discussed. The third part presents several case studies from recent and on-going drug discovery projects for a variety of target classes, from kinases and phosphatases to targeting protein-protein interaction and epigenetic targets.

This second edition further develops the principles of applying kinetic principles to drug metabolizing enzymes and transporters. Chapters are divided into six sections detailing fundamental principles of enzyme kinetics, enzyme and transporter structures, highlighting specific oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for drug metabolizing enzymes and transporters, understanding of variability both experimental and interindividual (pharmacogenomic), and expanded case studies that provide real life examples of applying these principles. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, in some cases step-by-step instructions with readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and fully updated, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications, Second Edition serves as a practical teaching tool for novice and advanced scientists interested in the fundamental concepts.

This is the most comprehensive treatise of this topic available, providing invaluable information on the technological and economic benefits to be gained from implementing continuous processes in the biopharmaceutical industry. Top experts from industry and academia cover the latest technical developments in the field, describing the use of single-use technologies alongside perfusion production platforms and downstream operations. Special emphasis is given to process control and monitoring, including such topics as 'quality by design' and automation. The book is supplemented by case studies that highlight the enormous potential of continuous manufacturing for biopharmaceutical production facilities.

Aging is an inevitable part of life and is becoming a worldwide social, economic and health problem. This is mainly due to the fact that the increasing proportion of individuals in the advanced age category have a higher probability of developing age-related disorders, such as type II diabetes mellitus, cardiovascular disorders, sarcopenia, and neurodegenerative conditions. New therapeutic approaches are still needed to decrease or slow the effects of such diseases. Advances in -omic technologies, such as genomics, transcriptomics, proteomics and metabolomics, have significantly advanced our understanding of disease in multiple medical areas, as the analysis of multiple molecular networks has simultaneously provided a more integrated view of disease pathways. It is hoped that emerging hits from these analyses might be prioritized for further screening as potential novel drug targets for increasing the human healthspan in line with the lifespan. In turn, this will lead to new therapeutic strategies as well as drug development projects by the pharmaceutical industry. This book presents a series of reviews describing studies that have resulted in identification of new potential drug targets for age-related disorders. Much of this information has come from -omic comparisons of healthy and disease states or from testing the effects of new therapeutic approaches. Authored by experts from around the globe, each chapter is presented in the context of specific chronic diseases or therapeutic strategies. This book is designed for researchers in the areas of aging and chronic disease, as well as clinical scientists, physicians and stakeholders in major drug companies.

Foreseeing and planning for all of the possibilities and pitfalls involved in bringing a biotechnology innovation from inception to widespread therapeutic use takes strong managerial skills and a solid grounding in biopharmaceutical research and development procedures. Unfortunately there has been a dearth of resources for this aspect of the field. Until now. Focusing on the management of healthcare-related biotech, from conception through the product's regulatory approval and entire life cycle, Healthcare Biotechnology: A Practical Guide provides a practical, applicable resource to assist all health-care related biotech professionals in their day-to-day activities from the lab to the boardroom. Divided into six sections, the book begins with current systems and recent progress and controversy, major players and products, and a comparison with the pharmaceutical industry. It covers intellectual property protection and management, the innovation cycle, patent application, commercialization, and competition. Coverage includes funding, partnering, cash-intensive activities, financing alternatives, and the complexities of alliance implementation and management. It highlights research, development, and biomanufacturing; and examines clinical trial design and regulations; "fast-track" approvals; and patient recruitment as well as production platforms and processes, costs, strategies, and timelines. It investigates marketing including planning, promotion, pricing, supply chain management, and bio-brand lifecycle management. It concludes with tips on running the business, offering diverse biobusiness models and reasonable expectations from inception through maturity and decline. An indispensible guide, this book offers more than 40 figures, 220 tables, and 180 references as well as a list of abbreviations and a business plan outline. Each chapter contains 10 questions to reinforce the material covered and 10 exercises

This book traces the evolution of the pharmacist from compounder-dispenser to advisor counselor. It explores the impact on pharmacy of broad sociologic, demographic, and economic trends and examines controversial issues such as professional versus business objectives, managed cost care, coginitive services, pharmaceutical care, and the future roles of pharmacists. Drawing on the literature in sociology and social pathology, the book relates some theoretical constructs to the changing roles of the pharmacist. It includes coverage of pharmaceutical education, disease state management, managed care, and new technologies.

This book explores technological innovation in family firms, seeking to reconstruct the links between the heterogeneous dimensions of family businesses and their innovative behaviour. Building on and examining the traditional view of family firms as conservative, this book contributes to knowledge surrounding the puzzling role of family firms in technological innovation, with particular focus on the Italian pharmaceutical industry. The authors explore technological advances within the industry in connection with various features of family governance. This thought-provoking study is divided into two parts, the first part providing an overview of current literature on the topic, and the second part analysing the findings of empirical investigation in a specific industry setting. Practitioners and academics of business strategy will find this book extremely useful as it combines both solid theoretical reasoning and robust empirical analysis.

This detailed book examines the main methods to study mammalian monoamine oxidases (MAOs), ranging from cell biology to computational chemistry. Beginning with techniques on how to obtain pure samples of MAO A and MAO B, the volume continues by covering assays and techniques used to measure MAO enzymatic activity and perform inhibition studies, methods to address cellular localization and function of MAOs, either in cell lines or in animal models, as well as computational methods applied to rational drug design approaches that are used to develop new MAO inhibitors. Written for the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Monoamine Oxidase: Methods and Protocols serves as a vital resource for scientists who are interested in studying MAOs and other similar amine oxidase enzymes.

Handbook of Essential Oils: Science, Technology, and Applications presents the development, use and marketing of essential oils. Exciting new topics include insecticidal applications, but there is a continued focus on the chemistry, pharmacology and biological activities of essential oils. The third edition unveils new chapters including the insect repellent and insecticidal activities of essential oils, the synergistic activity with antibiotics against resistant microorganisms, essential oil applications in agriculture, plant-insect interactions, and pheromones and contaminants in essential oils. Features Presents a wide range of topics including sources, production, analysis, storage, transport, chemistry, aromatherapy, pharmacology, toxicology, metabolism, technology, biotransformation, application, utilization, and trade Includes discussions of biological activity testing, results of antimicrobial and antioxidant tests, and penetration enhancing activities useful in drug delivery Covers up-to-date regulations and legislative procedures, together with the use of essential oils in perfumes, cosmetics, feed, food, beverages, and pharmaceutical industries Unveils new chapters including the insect repellent and insecticidal activities of essential oils, the synergistic activity with antibiotics against resistant microorganisms, essential oil applications in agriculture, plant-insect interactions, and pheromones and contaminants in essential oils The American Botanical Council (ABC) named the second edition as the recipient of the 2016 ABC James A. Duke Excellence in Botanical Literature Award and recognized that essential oils are one of the fastest growing segments of the herbal product market

This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.

Microbiologists working in both the pharmaceutical and medical device industries, face considerable challenges in keeping abreast of the myriad microbiological references available to them, and the continuously evolving regulatory requirements. The Handbook of Microbiological Quality Control provides a unique distillation of such material, by providing a wealth of microbiological information not only on the practical issues facing the company microbiologist today, but also the underlying principles of microbiological quality assurance. All the chapters have been written by leading experts in this field. The Handbook of Microbiological Quality Control provides guidance on safe microbiological practices, including laboratory design and sampling techniques. The design storage, use and quality control of microbiological culture is considered in depth. Principles of enumeration and identification of micro-organisms, using both traditional and rapid methods as well as the pharmacopoeial methods for the detection of specified organisms, are elaborated in detail. Guidance is given on laboratory methods supporting the sterility assurance system: sterility testing, bioburden testing, the use of biological indicators and environmental monitoring methods, as well as methods for detecting and quantifying endotoxins. Pharmacopoeial methods for microbiological assay and preservative efficacy testing are reviewed. Problems for those involved in disinfection and cleansing techniques and microbiological audit are discussed from a practical viewpoint. Finally, a number of pertinent case studies and worked examples illustrate problems highlighted in the text. The Handbook of Microbiological Quality Control is the essential reference source for the professional microbiologist.

This book offers a fresh look on a variety of issues concerning herbal medicine - the methods of growing and harvesting various medicinal plants; their phytochemical content; medicinal usage; regulatory issues; and mechanism of action against myriad of human and animal ailments. 'Medicinal Plants: From Farm to Pharmacy' comprises chapters authored by renowned experts from academics and industry from all over the world. It provides timely, in-depth study/analysis of medicinal plants that are already available in the market as supplements or drug components, while also introducing several traditional herbs with potential medicinal applications from various regions of the world. The book caters to the needs of a diverse group of readers: plant growers, who are looking for ways to enhance the value of their crops by increasing phytochemical content of plant products; biomedical scientists who are studying newer applications for crude herbal extracts or isolated phytochemicals; clinicians and pharmacologists who are studying interactions of herbal compounds with conventional treatment modalities; entrepreneurs who are navigating ways to bring novel herbal supplements to the market; and finally, natural medicine enthusiasts and end-users who want to learn how herbal compounds are produced in nature, how do they work and how are they used in traditional or modern medicine for various disease indications.

This book bridges the gap between practitioners of supply-chain management and pharmaceutical industry experts. It aims to help both these groups understand the different worlds they live in and how to jointly contribute to meaningful improvements in supply-chains within the globally important pharmaceutical sector. Scientific and technical staff must work closely with supply-chain practitioners and other relevant parties to help secure responsive, cost effective and risk mitigated supply chains to compete on a world stage. This should not wait until a drug has been registered, but should start as early as possible in the development process and before registration or clinical trials. The author suggests that CMC (chemistry manufacturing controls) drug development must reset the line of sight - from supply of drug to the clinic and gaining a registration, to the building of a patient value stream. Capable processes and suppliers, streamlined logistics, flexible plant and equipment, shorter cycle times, effective flow of information and reduced waste. All these factors can and should be addressed at the CMC development stage.

This book explains theoretical and technological aspects of amorphous drug formulations. It is intended for all those wishing to increase their knowledge in the field of amorphous pharmaceuticals. Conversion of crystalline material into the amorphous state, as described in this book, is a way to overcome limited water solubility of drug formulations, in this way enhancing the chemical activity and bioavailability inside the body. Written by experts from various fields and backgrounds, the book introduces to fundamental physical aspects (explaining differences between the ordered and the disordered solid states, the enhancement of solubility resulting from drugs amorphization, physical instability and how it can be overcome) as well as preparation and formulation procedures to produce and stabilize amorphous pharmaceuticals. Readers will thus gain a well-funded understanding and find a multi-faceted discussion of the properties and advantages of amorphous drugs and of the challenges in producing and stabilizing them. The book is an ideal source of information for researchers and students as well as professionals engaged in research and development of amorphous pharmaceutical products.

This book explores the possible development of neurokinin-3 receptor (NK3R) antagonists with reduced environmental impact. Pharmaceuticals are used to cure diseases and to alleviate symptoms in humans and animals. However, the stable, bioactive substances excreted by patients have unfavorable effects on non-target species. To overcome these disadvantages of these highly stable, potent substances, drug design to turn off bioactivity after release into the environment is needed. The book describes the development of eco-friendly NK3R antagonists by introducing a labile functional moiety and substituting a scaffold. This resulted in a novel NK3R antagonist that oxidized into its inactive form when exposed to air. Further, the book presents an efficient and easily achievable synthetic method of creating triazolopiperazine scaffolds, as well as a structure-activity relationship study involving scaffold hopping for decomposable motifs, which led to a novel photodegradable NK3R antagonist. Demonstrating that it is possible to develop compounds that convert into their inactive forms under environmental conditions, this book is useful for anyone interested in therapeutic agents with reduced environmental impact.

This book is a comprehensive review of thrombin, especially as regulatory protease. The ready availability of highly purified thrombin has stimulated rapid advances in the cell biology of this important macromolecule. The text focuses on research findings from the discovery of thrombin by Andrew Buchanan in 1842 to the present. A substantial amount of this work was conducted by the author and his colleagues. His work on the purification of thrombin was seminal to much subsequent work on thrombin. This volume provides a framework for future studies now made possible by the discovery of the importance of exosites in the physiology of thrombin function. The current work describes the process of the development of an oral inhibitor of thrombin used in the prevention of thrombosis. Key Features Reviews the history of Thrombin (Fibrin Ferment) Documents the relation of protein engineering and chemical modification in the study of thrombin Summarizes the interaction of thrombin with fibrinogen and fibrin Outlines the role of exosites in thrombin function Describes the development of an oral inhibitor for thrombin