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Author: Bernard Testa
Publisher: John Wiley & Sons
ISBN: 9783906390222
Category : Medical
Languages : en
Pages : 678
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Book Description
The optimization of pharmacokinetic properties has become the bottleneck and a major challenge in drug research. There was, hence, an urgent need for a book covering this field in an authoritative, comprehensive, factual, and conceptual manner. In this work of unique breadth and depth, international authorities and practicing experts from academia and industry present the most modern biological, physicochemical, and computational strategies to achieve optimal pharmacokinetic properties in research series. These properties include gastrointestinal absorption, protein binding, brain permeation, and metabolic profile. Toxicological issues are, of course, also of utmost importance. In addition to its 33 chapters, the book includes a CD-ROM containing the invited lectures, oral communications and posters (in full version) presented at the Second LogP Symposium, 'Lipophilicity in Drug Disposition -- Practical and Computational Approaches to Molecular Properties Related to Drug Permeation, Disposition and Metabolism', held at the University of Lausanne in March 2000.n̓.
Author: Bernard Testa
Publisher: John Wiley & Sons
ISBN: 9783906390222
Category : Medical
Languages : en
Pages : 678
Get Book Here
Book Description
The optimization of pharmacokinetic properties has become the bottleneck and a major challenge in drug research. There was, hence, an urgent need for a book covering this field in an authoritative, comprehensive, factual, and conceptual manner. In this work of unique breadth and depth, international authorities and practicing experts from academia and industry present the most modern biological, physicochemical, and computational strategies to achieve optimal pharmacokinetic properties in research series. These properties include gastrointestinal absorption, protein binding, brain permeation, and metabolic profile. Toxicological issues are, of course, also of utmost importance. In addition to its 33 chapters, the book includes a CD-ROM containing the invited lectures, oral communications and posters (in full version) presented at the Second LogP Symposium, 'Lipophilicity in Drug Disposition -- Practical and Computational Approaches to Molecular Properties Related to Drug Permeation, Disposition and Metabolism', held at the University of Lausanne in March 2000.n̓.
Author: Rajesh Krishna
Publisher: CRC Press
ISBN:
Category : Medical
Languages : en
Pages : 328
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Book Description
This reference provides a concise overview of the key principles in dose selection and optimization and demonstrates applicability to recent successful new drug applications. Compiling key issues and current research on safety, efficacy, and clinical pharmacology, and PK-PD, this volume critically highlights the multidisciplinary nature of drug development and spans the fields of pharmacokinetics, clinical pharmacology, biostatistics, and experimental medicine.
Author: Gary W. Caldwell
Publisher: Humana
ISBN: 9781493960705
Category : Medical
Languages : en
Pages : 0
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Book Description
Thoroughly revised and updated, Optimization in Drug Discovery: In Vitro Methods, Second Edition presents a wide spectrum of in vitro assays including formulation, plasma binding, absorption and permeability, cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) metabolism, CYP inhibition and induction, drug transporters, drug-drug interactions via assessment of reactive metabolites, genotoxicity, and chemical and photo-mutagenicity assays. Written for the Methods in Pharmacology and Toxicology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Expert authors have developed and utilized these in vitro assays to achieve “drug-like” characteristics in addition to efficacy properties and good safety profiles of drug candidates. Comprehensive and up-to-date, Optimization in Drug Discovery: In Vitro Methods, Second Edition aims to guide researchers down the difficult path to successful drug discovery and development.
Author: Dennis A. Smith
Publisher: John Wiley & Sons
ISBN: 3527608281
Category : Medical
Languages : en
Pages : 207
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Book Description
In this new edition of a bestseller, all the contents have been updated and new material has been added, especially in the areas of toxicity testing and high throughput analysis. The authors, all of them employed at Pfizer in the discovery and development of new active substances, discuss the significant parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. They cover everything from the fundamental principles right up to the impact of pharmacokinetic parameters on the discovery of new drugs. While aimed at all those dealing professionally with the development and application of pharmaceutical substances, the readily comprehensible style makes this book equally suitable for students of pharmacy and related subjects.
Author: Bernard Testa
Publisher: Wiley-VCH
ISBN: 9783906390352
Category : Science
Languages : en
Pages : 500
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Book Description
Informatics and robotics are the workhorses of a technological revolution in drug research. On them are based combinatorial chemistry, which yields compounds by the many thousands, and high-throughput bioassays, which screen them for activity. The results are avalanches of 'hits', which invade the databases like swarms of locusts. But far from being a plague, these innumerable compounds become a blessing if properly screened for 'drugability', i.e., for 'drug-like' properties such as good pharmacokinetic (PK) behavior. Pharmacokinetic profiling of bioactive compounds has, thus, become a sine qua non condition for cherry-picking the most promising hits. Just as important, but less visible, are the structure-property and structure-ADME relations, which emerge from PK profiling and provide useful feedback when designing new synthetic series. As a result, the screening, design, and optimization of pharmacokinetic properties has become the bottleneck and a major challenge in drug research. To shorten the time-consuming development and high rate of attrition of active compounds ultimately doomed by hidden pharmacokinetic defects, powerful biological, physicochemical, and computational approaches are being developed, whose objectives are to increase the clinical relevance of drug design and to eliminate as soon as possible compounds with unfavorable physicochemical properties and pharmacokinetic profiles. The profiling of ADME properties (absorption, distribution, metabolism, and excretion) is the topic of this book. Following the extraordinary success of the previous work ('Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical, and Computational Strategies', Eds. B. Testa, H. van de Waterbeemd, G. Volkers, R. Guy, Verlag Helvetica Chimica Acta, Zürich, 2001, 655 pages), there was a need for an essentially new edition focusing on the latest theoretical and technological breakthroughs. In this unique work, international authorities and practicing experts from academia and industry offer state-of-the-art presentations of concepts, methods and technologies now in use or development in drug research. The biological strategies emphasized in the book include cell cultures, drug-metabolizing enzymes, transporters and plasma protein binding. The physicochemical strategies focus on artificial membrane-permeability assays, on solubility and lipophilicity and related molecular properties as factors and predictors of pharmacokinetic behavior, and on stability and solid-state properties. Computational strategies comprize the exploration of property spaces, pharmacophore searching to predict biotransformation and enzyme inhibition, and expert systems to process biopharmaceutical profiling data. In addition to its 28 chapters, the book includes a CD-ROM containing the invited lectures, oral communications, and posters (in full version) presented at the Third LogP Symposium, 'Physicochemical and Biological Profiling in Drug Research', held at the Federal Institute of Technology (ETH) of Zürich in March 2004.
Author: Li Di
Publisher: Academic Press
ISBN: 0128013222
Category : Medical
Languages : en
Pages : 582
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Book Description
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will successfully complete human Phase I clinical trials. Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition, provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property. Through valuable case studies, structure-property relationship descriptions, and structure modification strategies, Drug-Like Properties, Second Edition, offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization. Provides a comprehensive and valuable working handbook for scientists and students in medicinal chemistry Includes expanded coverage of pharmacokinetics fundamentals and effects Contains updates throughout, including the authors’ recent work in the importance of solubility in drug development; new and currently used property methods, with a reduction of seldom-used methods; and exploration of computational modeling methods
Author: James R. Empfield
Publisher: Springer
ISBN: 366243914X
Category : Science
Languages : en
Pages : 176
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Book Description
Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.
Author: Li Di
Publisher: Elsevier
ISBN: 0080557619
Category : Science
Languages : en
Pages : 549
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Book Description
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. Serves as an essential working handbook aimed at scientists and students in medicinal chemistry Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies Discusses improvements in pharmacokinetics from a practical chemist's standpoint
Author: Zhengyin Yan
Publisher: Humana Press
ISBN: 9781588293329
Category : Medical
Languages : en
Pages : 420
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Book Description
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.
Author: Florencio Zaragoza Dörwald
Publisher: John Wiley & Sons
ISBN: 352733226X
Category : Science
Languages : en
Pages : 627
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Book Description
Small structural modifications can significantly affect the pharmacokinetic properties of drug candidates. This book, written by a medicinal chemist for medicinal chemists, is a comprehensive guide to the pharmacokinetic impact of functional groups, the pharmacokinetic optimization of drug leads, and an exhaustive collection of pharmacokinetic data, arranged according to the structure of the drug, not its target or indication. The historical origins of most drug classes and general aspects of modern drug discovery and development are also discussed. The index contains all the drug names and synonyms to facilitate the location of any drug or functional group in the book. This compact working guide provides a wealth of information on the ways small structural modifications affect the pharmacokinetic properties of organic compounds, and offers plentiful, fact-based inspiration for the development of new drugs. This book is mainly aimed at medicinal chemists, but may also be of interest to graduate students in chemical or pharmaceutical sciences, preparing themselves for a job in the pharmaceutical industry, and to healthcare professionals in need of pharmacokinetic data.
