The young investigator with an idea has to negotiate many institutional, federal, and industrial challenges in order to get a product to market. Nowhere is described the steps in the development of new drugs, diagnos tics, or devices; the person with an idea has nowhere to turn for information and details. The young investigator may understand the elements of basic and clinical research, but ordinarily has no insight into novel ways of finding research funding or how to explore to find the funding opportunities that are available. The young investigator has little knowledge of the mecha nisms to bring an idea through the developmental phases to the market. There are other players in this complex endeavor with whom he or she has no contact, including those from industry, the Food and Drug Administration, and the legal community. Exposure to the philosophy of product develop ment and to procedural information would be useful to the scientific com munity, as would contact with those who have successfully taken an idea to a finished product. A first attempt to do this was the symposium on Idea to Product: The Process, sponsored by Serono Symposia USA and held No vember 17 to 20, 1994, in Washington, D.C. This book comprises the pro ceedings of that meeting. The editors are indebted to the many contributors to this volume, and we are especially grateful to Serono Symposia USA and to Leslie Nies and her staff for their expertise in organizing the symposium."

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

Extracted from the Drug Abuse Handbook, 2nd edition, to give you just the information you need at an affordable price. Forensic Issues in Alcohol Testing offers concise and focused information specific to the interests of forensic scientists and clinical and forensic toxicologists. It analyzes the acute effects of alcohol intoxication and the methods by which investigators can measure alcohol concentration in blood, urine, and breath. It considers extenuating circumstances affecting acute impairment by detailing the disposition and fate of alcohol in the body as well as the factors influencing absorption, distribution, and elimination. Specific chapters address difficulties in measuring and interpreting post-mortem alcohol concentrations due to poor quality of specimen, sampling site differences, and post-mortem diffusion or synthesis. Recent advances in biochemical testing make it possible to quantitate chronic alcohol ingestion, and the book analyzes the efficacy of these tests as evaluators of dependence or potential for dependence.

Extracted from the Drug Abuse Handbook, 2nd edition, to give you just the information you need at an affordable price.

Pharmacokinetics and Pharmacodynamics of Abused Drugs is a concise and focused volume devoted to the metabolism and measurable effects of drugs on the human body. Beginning with basic concepts and models designed to provide a fundamental understanding of the subject matter, the book details the specifics of absorption, distribution, and elimination pathways and rates of commonly abused drugs. It analyzes the effects of drug use on human performance including response time, memory and recall, logical and cognitive processes, as well as physiological changes. Packed with data and comparative studies, this handy volume considers the effects of marketed and prescription medications as well as illicit drugs including opioids, cannabis, cocaine, methamphetamine, MDMA, ketamine, nicotine, and LSD. Containing 29 figures and tables and extensive references, this is a must-have resource for the influence of drug use and abuse on human physiology and performance.

"Frank discussions of opportunities and challenges point the way to new, more effective drug delivery systems"

Interest in nanomedicine has grown tremendously, fueled by the expectation that continued research will lead to the safe, efficient, and cost-effective delivery of drugs or imaging agents to human tissues and organs. The field, however, has faced several challenges attempting to translate novel ideas into clinical benefits. With contributions from an international team of leading nanomedicine researchers, this book provides a practical assessment of the possibilities and the challenges of modern nanomedicine that will enable the development of clinically effective nanoparticulate drug delivery products and systems.

"Nanoparticulate Drug Delivery Systems" focuses on the rationales and preclinical evaluation of new nanoparticulate drug carriers that have yet to be thoroughly reviewed in the literature. The first chapter sets the stage with a general overview of targeted nanomedicine. The book then explores new and promising nanoparticulate drug delivery systems, including: Lipid nanoparticles for the delivery of nucleic acidsMultifunctional dendritic nanocarriersPolymer drug nanoconjugates

Next, the book presents new opportunities and challenges for nanoparticulate drug delivery systems, including: Clearance of nanoparticles during circulationDrug delivery strategies for combatting multiple drug resistanceToxicological assessment of nanomedicine

Chapters offer state-of-the-technology reviews with extensive references to facilitate further investigation. Moreover, each chapter concludes with an expert assessment of remaining challenges, pointing the way to solutions and new avenues of research.

With its frank discussions of opportunities and challenges, "Nanoparticulate Drug Delivery Systems" sets a solid foundation for new research leading to the discovery and development of better nanomedicines.

This user-friendly resource offers complete and comprehensive coverage of the difficult challenges posed by drug-drug interactions. Over 170 case vignettes illustrate a variety of interactions (DDIs) to provide an unintimidating -- even entertaining -- approach to understanding these issues. Drug-Drug Interaction Primer builds on the author's earlier work, Drug Interactions Casebook: The Cytochrome P450 System and Beyond, and features updated references throughout and 29 new cases that provide such clinical examples as: a patient diagnosed with schizoaffective disorder transitions from haloperidol to aripiprazole with disastrous results; an AIDS patient's trimethoprim-sulfamethoxazole is replaced with warfarin following atrial fibrillation, resulting in ischemic stroke; and a delusional patient on risperidone is placed on phenytoin following seizures, and delusions return. Previous cases have been revised to enhance clarity.

An introduction to core concepts, which includes brief reviews of each enzyme system, brings the reader up to speed on how to think about DDIs and begin to grapple with what might seem like an imposing subject. The vignettes that follow each include a case presentation and an explanation of the mechanism by which the interaction(s) occurred, and each derives from sound clinical evidence -- not merely extrapolations from drug characteristics -- to offer a more realistic understanding of DDIs. Most of the interactions described involve the cytochrome P450 enzyme system; others involve alterations in phase II metabolism and P-glycoprotein functioning, as well as plasma protein displacement effects. The appendices detail most drug-drug interactions between psychotropic agents and contain metabolic pathways and inhibitory and inductive profiles for antidepressants, antipsychotics, and mood stabilizing agents -- as well as tables that detail all known and clinically significant DDIs between pairings of any two agents from these drug classes. An extensive index allows quick reference. Among the book's other features: - Reorganization by medical subspecialty -- psychiatry, internal medicine, neurology, surgery/anesthesia, and gynecology, oncology, and dermatology -- better facilitates clinical application.- Comprehensive tables detail substrates, inhibitors, and inducers for P450, phase II, and P-glycoprotein. - DDIs involving select nonpsychotropic agents such as tobacco, ethinylestradiol, and statins.- Exploration of the paradigm of plasma protein binding mediated DDIs in detail, with cases conveniently indexed.

These cases bring DDIs alive in a way that drier descriptions cannot, and this volume introduces more original material than will be found in other sources. Drug-Drug Interaction Primer is brimming with material that can be put to immediate use, offering insights that will improve any practitioner's skills.

In this book we present recent studies that have been carried out on some widely used medicinal plants. The need for new and alternative treatments stem from the lack of efficiency of existing remedies for certain illnesses. We have compiled information that may be useful to researchers in their quest to develop new drugs.

Research into the processes of tolerance and sensitization has escalated at a substantial rate in recent years, presumably because of the fundamental importance of understanding the long-term, as opposed simply to the initial, acute effects of drugs. The rapid of such research in recent years is documented c1early by growth the editors in the introductory chapter to this text. However, despite the fact that there is a very large amount of literature concemed with the effects of long-term drug treatment, there is, to the best of our knowledge, no published text that has ever attempted to integrate some of the many diverse findings that have been made in this area. Basic research has uncovered a num ber of different mechanisms by which tolerance and sensitization to drugs can develop. Such mechanisms are of very different types, involving psychological behavioral, metabolic, neuronal, and subcellular processes. Because of the complexity of each of these different types of mechanisms, with few exceptions, individual re searchers usually tend, understandably, to concentrate on their own specific areas of expertise, paying relatively little attention to rele vant research occurring in other areas. Consequently, they neglect or simply ignore the important question of the relative importance of the specific mechanism that they are studying, and the related question of the possible interrelationships that may exist between different mechanisms for the production of tolerance and sensitiza tion."

Tamoxifen has persisted as a widely accepted and administered drug for almost 25 years. Following the many scientific papers and books on the subject, it has remained a very intriguing substance. This, perhaps, is the reason for another monograph on Tamoxifen. It is regrettably true that overviews, even when up to date after exhaustive research - the shibboleth of our cultures -, rapidly lose relevance with the passage of time. Scientists can sometimes be pictured as deep sea divers, who plunge into the unknown in search of a hitherto unknown world. Their descent is exciting, but eventually they must come up for air and integrate their experiences with others who also had to resurface. This book intends to collect and, where possible, to collate recent, but sometimes seemingly unrelated information. To quote Stephane Mallarme: "Everything in the world exists to end up in a book." Even if this is a tad cynical, it might not be far from the truth. If a little knowledge is a dangerous commodity, one can also add - tongue in cheek - that a vast amount of knowledge can be truly hazardous. It is likely that what might seem as entangled data is confusing, especially for those satisfied with the comfortable interpretation of Tamoxifen as an antiestrogen which has long been found insufficient. The complexity of its mechanisms and effects defies simple explanations and may even seem capricious, but only because of our ignorance.

The clinical microbiology laboratory is often a sentinel for the detection of drug resistant strains of microorganisms. Standardized protocols require continual scrutiny to detect emerging phenotypic resistance patterns. The timely notification of clinicians with susceptibility results can initiate the alteration of antimicrobial chemotherapy and improve patient care. It is vital that microbiology laboratories stay current with standard and emerging methods and have a solid understanding of their function in the war on infectious diseases. Antimicrobial Susceptibility Testing Protocols clearly defines the role of the clinical microbiology laboratory in integrated patient care and provides a comprehensive, up-to-date procedural manual that can be used by a wide variety of laboratorians. The authors provide a comprehensive, up-to-date procedural manual including protocols for bioassay methods and molecular methods for bacterial strain typing. Divided into three sections, the text begins by introducing basic susceptibility disciplines including disk diffusion, macro and microbroth dilution, agar dilution, and the gradient method. It covers step-by-step protocols with an emphasis on optimizing the detection of resistant microorganisms. The second section describes specialized susceptibility protocols such as surveillance procedures for detection of antibiotic-resistant bacteria, serum bactericidal assays, time-kill curves, population analysis, and synergy testing. The final section is designed to be used as a reference resource. Chapters cover antibiotic development; design and use of an antibiogram; and the interactions of the clinical microbiology laboratory with the hospital pharmacy, and infectious disease and control. Unique in its scope, Antimicrobial Susceptibility Testing Protocols gives laboratory personnel an integrated resource for updated lab-based techniques and charts within the contextual role of clinical microbiology in modern medicine.

This volume thoroughly covers HIV-1 antiretrovirals currently in clinical use, together with their advantages and limitations. HIV-1 inhibitor resistance is discussed in detail, and critical assessments as to what will be required of future antiretrovirals in order to halt viral replication, reduce viral resistance, and alter the state of viral latency are presented. Experts at the forefront of HIV-1 research provide overviews of approaches from the fields of virology, chemical biology and structural biology for obtaining small molecule inhibitors that target viral regulatory and structural components at multiple points in the viral lifecycle. The individual chapters will appeal to scientists and clinicians alike.

This book was tbe result of a symposium beld at tbe American Cbernical Society meeting in Miami Beacb, Florida, September 10-15, 1989. The symposium was jointly sponsored by Tbe Society for Economfc Botany and tbe American Cbernical Society Food and Natural Product sub division. Tbere were five speakers. During tbe social sessions (mostly over drinks in abotel room), it became obvious tbat, regardless of tbe discipline, we were all speaking tbe same language. Yet, prior to tbe symposium, only a few of tbe participants knew one anotber. We decided to expand tbe symposium into a book. The book would, we boped, accomplish for otbers wbat we bad discovered in ourselves. That is, the field of Natural Products is broad, but similar in techniques and approach, ancient but modern, and bas been and continues to be extremely valuable to humankind. We wanted the book to serve as an introductory text for courses and as a reference work for the future. We also determined to include the structure of every chemical in the chapter where it was mentioned so the reader would not have to find the structure somewhere else or to try and deduce the structure from the chemical name. Little did we know what an undertaking these goals would be or the time this would take.

In my professional career as a pharmaceutical scientist, I have been involved with severalaspectsofthe drugdevelopmentprocessfrompre-INDto commercialization and, somehow, I usually found myself coming back to a stability-related issue. The stability area seemed to draw my utmost interest because in my day-to-day work, my opportunities involved more than one product, and none of the issues were the same.Eachsituationposedchallengesthatusuallyrequiredanexerciseofjudgment, an understandingof regulations, a knowledgeof science, a graspof compliance, and an appreciation of common practices. Sinceearly2000, Ihavealsobeeninvolvedwithseveraltrainingopportunitiesand I struggled to ?nd good, concise, practical resources, one of which I could just hand to a new scientist who wishes to gain a greater understanding of stability sciences. In addition, I encountered the same questions posted over and over on different stability best practices discussion forums. As a book lover, I also have a good collection of technical books. Unfor- nately, most of the stability related volumes are outdated. Many of these materials are theoretical and do not contain much practical information. I understand that the pharmaceutical industry during this period is quite volatile, and guidelines are changingrapidlywhileregulatoryagenciesareworkingcloselywiththepharmac- tical industryto accommodatethese changes;however, thefundamentalinformation continues to remain quite the same, just as current Good Manufacturing Practices (cGMP) continue to be the standard industry practice. Therefore, I hoped to ass- ble a practical handbook to ?ll this v

Focused more specifically on the recent advances in applications of various metals and their complexes used in biomedicine, particularly in the diagnosis and treatment of chronic diseases. The editors give equal importance to other key aspects such as toxicological issues and safety concerns. The application of metals in the biomedical field is highly interdisciplinary and has a broad appeal across all biomedical specialties. Biomedical Applications of Metals is particularly focused on covering the role of metals in medicine and the development of novel therapeutic products and solutions in the form of alternative medicines, and some topics on Indian traditional medicine i.e., "Ayurveda". In Section I, the book discusses the role of metals in medicines and include chapters on nanoparticles, noble metals, medical devices, copper. selenium, silver, and microbial pathogens; while Section II includes topics on metals toxicity including heavy metals, carcinogens, cancer therapy, Bhasma's and chelating agents used in Ayurveda, and biochemical and molecular targets including actions of metals. These new and emerging concepts of applications of metals in medicine, their crucial role in management of microbial resistance, and their use in the treatment of various chronic diseases is essential information for toxicologists, and clinical and biomedical researchers.

The formation of drug policy is a complex phenomena influenced by a multi tude of sources. Among others, these influences include historical factors, contemporary public opinion regarding the nature and magnitude of drug use and abuse, the portrayal of illicit drugs and drug use in the media, and lobbying efforts by special interest groups (e. g. , The Drug Policy Foundation), including government agencies (e. g. , the Justice Department and law enforcement). An additional source of influence are the activities of specialists directly engaged in studying drug use and treating drug dependence. This includes individuals involved in drug treatment, anthropological and cultural studies, policy analy ses, basic psychological and pharmacological research, research on the epide miology of drug use and dependence, and research on prevention. This influ ence by specialists might be usefully distinguished from those influences first mentioned for two reasons: First, studies of drug use and dependence attempt to uncover empirical generalizations about drugs, and second, because these findings are empirical, there is a hope that they guide, at least to some extent, the actions of other forces that more directly determine drug policy. Psychology as an empirical discipline has long been interested in the use of psychoactive drugs. At the level of basic science in psychopharmacology, a most important contribution has been the demonstration that drugs of abuse function as reinforcers and thus enter into the same psychological processes as do other appetitive stimuli.

From the President of the American Society of Addiction Medicine Recent Developments in Alcoholism (Volume 10) is a major contribution to the literature of addiction medicine. This volume, 'ru.cohol and Cocaine: Similarities and Differences," contains an impressive collection of chapters from the basic research, epidemiological, and clinical research perspectives, as well as articles that address the relative policy issues and clinical application and patient care concerns. It also sends a message to those who would still distinguish between alcohol and drugs, or legal and illegal drugs. In the research laboratory, in the intentions and behavior of the user, and by the clinician, such distinctions have never been upheld. The first section, "Clinical Pathology," includes chapters on the role of alcohol in cocaine dependence, dual-diagnosis empirical and developmental humanistic approaches, and on neuroendocrine and catecholamine levels in humans during administration and withdrawal of cocaine and alcohol, emer gency room evaluation of cocaine-associated neuropsychiatric disorders, and clinical and pharmacological interactions of alcohol and cocaine. These chap ters, written by authors who are preeminent in their fields, offer a broad perspective to both the researcher and the clinician on relevant issues in clinical pathology. ."

Western Medicine as seen today has a strong scientific basis in its development. The pathogenesis of most diseases and their symptomatology and physical signs are well studied and understood. The management of patients is based on firm understanding of these disease processes. In contrast, Traditional Chinese Medicine came about through the experience of many generations of practitioners over thousands of years. Undoubtedly, many of these treatments have proved to be effective in their own way, however, firm scientific basis is still lacking.

While most Western Medicine advocates control of disease by eradication of pathogens and surgical removal of diseased organs as in the case of cancer, Traditional Chinese Medicine seeks to improve resistance against disease. There is probably a great wealth of therapeutic value in Traditional Chinese Medicine, which has not been discovered or explored fully. By combining the knowledge of both Western and Traditional Chinese Medicine, one might be able to improve the results of efficacy of treatments and the survival of patients. The integration of Medicine from East and West will take time to evolve and will need interested physicians from different parts of the world to work closely together to realize such a possibility.

This book is an attempt to bridge the medical world of two great and ancient civilizations in their approach to the treatment of disease. It is informative with a detailed account of the history of medical development. It is highly recommended for those medical practitioners from both East and West who are interested to explore alternative medicine and research new areas of the medical frontier.

In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene receptor subtypes, exemplified by the cloning of the LTB4 receptor earlier this year. Coupled with this there has been a continued elucidation of signal transduction mechanisms underlying receptor activation. Consequent upon these advances has been the development of potent antagonists of the CysLT receptor, J and both these and inhibitors of leukotriene biosynthesis have entered clinical practice in the therapy of asthma. In this clinical setting antagonists of the CysLTJ receptor have been shown to be an effective therapy in chronic asthmatics, against antigen- and exercise-induced bronchoconstriction, and in aspirin-intolerant asthmatics. The advent of this new class of agents promises to change the way in which asthmatic patients are currently treated."

'Each topic is covered in sufficient depth, currency, and clarity to be of value to the neophyte and the seasoned researcher/clinician.' --- American Journal of Psychiatry, from a review of a previous volume The current volume addresses a range of issues across this diverse field, including the effects on society, physiology and biochemistry, clinical pathology, and trends in treatment.

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.

In the pharmaceutical industry, the incorporation of the disciplines of pharma- kinetics, pharmacodynamics, and drug metabolism (PK/PD/DM) into various drug development processes has been recognized to be extremely important for approp- ate compound selection and optimization. During discovery phases, the identifi- tion of the critical PK/PD/DM issues of new compounds plays an essential role in understanding their pharmacological profiles and structure-activity relationships. Owing to recent progress in analytical chemistry, a large number of compounds can be screened for their PK/PD/DM properties within a relatively short period of time. During development phases as well, the toxicology and clinical study designs and trials of a compound should be based on a thorough understanding of its PK/PD/DM properties. During my time as an industrial scientist, I realized that a reference work designed for practical industrial applications of PK/PD/DM could be a very valuable tool for researchers not only in the pharmacokinetics and drug metabolism departments, but also for other discovery and development groups in pharmaceutical companies. This book is designed specifically for industrial scientists, laboratory assistants, and managers who are involved in PK/PD/DM-related areas. It consists of thirteen chapters, each of which deals with a particular PK/PD/DM issue and its industrial applications. Chapters 3 and 12 in particular address recent topics on higher throughput in vivo exposure screening and the prediction of pharmacokinetics in humans, respectively. Chapter 8 covers essential information on drug metabolism for industrial scientists.

The role of orthography in reading and writing is not a new topic of inquiry. For example, in 1970 Venezky made a seminal contribution with The Structure of English Orthography in which he showed how both sequential redundancy (probable and permissible letter sequences) and rules of letter-sound correspondence contribute to orthographic structure. In 1972 Kavanagh and Mattingly edited Language by Eye and by Ear which contained important linguistic studies of the orthographic system. In 1980 Ehri introduced the concept of orthographic images, that is, the representation of written words in memory, and proposed that the image is created by an amalgamation of the word's orthographic and phonological In 1981 Taylor described the evolution of properties. orthographies in writing systems-from the earliest logographies for pictorial representation of ideas to syllabaries for phonetic representation of sounds to alphabets for phonemic representation of sounds. In 1985 Frith proposed a stage model for the role of orthographic knowledge in development of word recognition: Initially in the logographic stage a few words can be recognized on the basis of partial spelling information; in the alphabetic stage words are recognized on the basis of grapheme-phoneme correspondence; in the orthographic stage spelling units are recognized automatically without phonological mediation. In 1990 Adams applied connectionism to an analysis of the orthographic processing of skilled readers: letter patterns emerge from the association units linking individual letters.

Although numerous studies have been made of the Western educated political elite of colonial Nigeria in particular, and of Africa in general, very few have approached the study from a perspective that analyzes the impacts of indigenous institutions on the lives, values, and ideas of these individuals. This book is about the diachronic impact of indigenous and Western agencies in the upbringing, socialization, and careers of the colonial Igbo political elite of southeastern Nigeria. The thesis argues that the new elite manifests the continuity of traditions and culture and therefore their leadership values and the impact they brought on African society cannot be fully understood without looking closely at their lived experiences in those indigenous institutions where African life coheres. The key has been to explore this question at the level of biography, set in the context of a carefully reconstructed social history of the particular local communities surrounding the elite figures. It starts from an understanding of their family and village life, and moves forward striving to balance the familiar account of these individuals in public life, with an account of the ongoing influences from family, kinship, age grades, marriage and gender roles, secret societies, the church, local leaders and others. The result is not only a model of a new approach to African elite history, but also an argument about how to understand these emergent leaders and their peers as individuals who shared with their fellow Africans a dynamic and complex set of values that evolved over the six decades of colonialism.