Author: Bernard Testa
Publisher: Wiley-VCH
ISBN: 9783906390468
Category : Science
Languages : en
Pages : 0
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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, Z?rich, 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 Z?rich in March 2004.
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: Ronald Borchardt
Publisher: Springer Science & Business Media
ISBN: 9780971176799
Category : Medical
Languages : en
Pages : 512
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Book Description
This volume focuses on how to increase the efficiency of drug discovery and development. It is written by experienced discovery scientists from diverse disciplines, including chemistry, drug metabolism, and development sciences. The volume details in silico, in vitro, and in vivo tools for prediction, measurement, and application of compound properties to select and improve potential drug candidates.
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: Peter L. Bonate
Publisher: Springer Science & Business Media
ISBN: 9780971176744
Category : Medical
Languages : en
Pages : 648
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Book Description
These volumes are designed to be the most complete guide to pharmacokinetics (PK) and its role in drug development. They fill a gap between the academic science and the practical application of that knowledge in drug development. Volume 1 discusses the role that PK plays in selected clinical study designs. Volume 2 details the key regulatory and development paradigms in which PK supplements decision-making during drug development.
Author: Ronald D. Schoenwald
Publisher: CRC Press
ISBN: 1420010085
Category : Medical
Languages : en
Pages : 430
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Book Description
Pharmacokinetics has evolved from its origin into a complex discipline with numerous subspecialties and applications in patient management, drug development, and regulatory issues. This expansion has made it difficult for any one individual to become a full-fledged expert in all areas. Fulfilling the need for a wide-ranging guide to the many existi
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: Vishwanath Gaitonde
Publisher: BoD – Books on Demand
ISBN: 1789239753
Category : Medical
Languages : en
Pages : 166
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Book Description
The process of drug discovery and development is a complex multistage logistics project spanned over 10-15 years with an average budget exceeding 1 billion USD. Starting with target identification and synthesizing anywhere between 10k to 15k synthetic compounds to potentially obtain the final drug that reaches the market involves a complicated maze with multiple inter- and intra-operative fields. Topics described in this book emphasize the progresses in computational applications, pharmacokinetics advances, and molecular modeling developments. In addition the book also contains special topics describing target deorphaning in Mycobacterium tuberculosis, therapy treatment of some rare diseases, and developments in the pediatric drug discovery process.
Author: Lawrence Kruger
Publisher: CRC Press
ISBN: 1439812101
Category : Health & Fitness
Languages : en
Pages : 458
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Book Description
One of the Most Rapidly Advancing Fields in Modern Neuroscience The success of molecular biology and the new tools derived from molecular genetics have revolutionized pain research and its translation to therapeutic effectiveness. Bringing together recent advances in modern neuroscience regarding genetic studies in mice and humans and the practical
Author: Bernard Testa
Publisher: Wiley-VCH
ISBN: 9783906390352
Category : Science
Languages : en
Pages : 0
Get Book Here
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, Zurich, 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 Zurich in March 2004.
