Admet for Medicinal Chemists

A Practical Guide
Herausgegeben von Tsaioun, Katya; Kates, Steven A.

• Gebundenes Buch

Produktbeschreibung

Early ADMET explained: an integrated approach to successful drug development
This practical guide provides medicinal chemists insights into the field of early ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicology), giving them a how-to for implementing early ADMET testing in their workflows, and maximizing the success of drug candidates in preclinical and clinical studies.
The emphasis and themes illustrate the required collaboration and communication between team members from different specialties, such as chemists, biologists, formulators, toxicologists, and preclinical and clinical development specialists. The book demonstrates how this collaborative approach addresses long-standing productivity issues in the pharmaceutical industry, accelerates positive results, and helps improve the commercialization rate for therapeutic agents.
Written by a group of experts from diverse disciplines, ADMET for Medicinal Chemists covers all key areas of the drug development process, including:
Technical considerations when selecting preclinical drug candidates
Guidelines for how to avoid pitfalls during drug design and discovery
Proven cutting-edge approaches to preclinical studies and drug design
Essential computer methods for designing molecules with desired properties
Absorption and physicochemical properties of New Chemical Entities (NCE)
The concepts underlying pharmacokinetics
Assays for testing cardiac safety, genetic toxicity, and hepatic toxicity
In vivo toxicological considerations and complying with FDA requirements

Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 512
• Altersempfehlung: 8 bis 12 Jahre
• Erscheinungstermin: 1. März 2011
• Englisch
• Abmessung: 243mm x 165mm x 35mm
• Gewicht: 919g
• ISBN-13: 9780470484074
• ISBN-10: 0470484071
• Artikelnr.: 31199162

Autorenporträt

KATYA TSAIOUN, PhD, is Chief Scientific Officer of Cyprotex and, previously, president and founder Apredica, which was acquired by Cyprotex. Both companies specialize in the rapid preclinical in vitro assessment of the ADME-Tox (Absorption, Distribution, Metabolism, Elimination, and Toxicity) properties of small-molecule and peptide therapeutics. STEVEN A. KATES, PhD is Vice President of Research and Development at Ischemix. He is a highly experienced chemist with over twenty years in R&D for both life science products and human therapeutics, and has advanced several compounds through drug development from early preclinical to early clinical development. He has more than 100 patents and publications, including one book.

Inhaltsangabe

Preface. Contributors. 1 Introduction (Corinne Kay). 1.1 Introduction. 1.2
Voyage Through The Digestive System. 1.3 The Liver Metabolism. 1.4 The
Kidneys. 1.5 Conclusions. 2 In Silico ADME/Tox Predictions (David Lagorce,
Christelle Reynes, Anne-Claude Camproux, Maria A. Miteva, Olivier
Sperandio, and Bruno O. Villoutreix). 2.1 Introduction. 2.2 Key Computer
Methods for ADME/Tox Predictions. 2.3 Preparation of Compound Collections
and Computer Programs, Challenging ADME/Tox Predictions and Statistical
Methods. 2.4 ADME/Tox Predictions within Pharmaceutics Companies. 2.5
Challenging ADME/Tox Predictions. 2.6 Statistical Methods. 2.7 Conclusions.
3 Absorption and Physicochemical Properties of the NCE (Jon Selbo and
Po-Chang Chiang). 3.1. Introduction. 3.2. Physicochemical Properties. 3.3.
Stability. 3.4. Dissolution and Solubility. 3.5. Solid State. 4 ADME
(Martin E. Dowty, Dean M. Messing, Yurong Lai, and Leonid (Leo) Kirkovsky).
4.1 Introduction. 4.2 Absorption. 4.3 Distribution. 4.4 Elimination. 4.5
Drug Interactions. 4.6 Strategies for Assessing ADME Properties. 4.7 Tool
Summary for Assessing ADME Properties. 5 Pharmacokinetics for Medicinal
Chemists (Leonid (Leo) Kirkovsky and Anup Zutshi). 5.1 Introduction. 5.2
ADME. 5.3 The Mathematics of Pharmacokinetics. 5.4 Drug Administration and
PK Observations. 5.5 Human PK Projection. 5.6 PK Practices. 5.7 Engineering
Molecules with Desired ADME Profile. 6 Cardiac Toxicity (Ralf Kettenhofen
and Silke Schwengberg). 6.1 Introduction. 6.2 Ion Channel-Related Cardiac
Toxicity. 6.3 Nonarrhythmic Cardiac Toxicity. 7 Genetic Toxicity: In Vitro
Approaches for Medicinal Chemists (Richard M. Walmsley and David Elder).
7.1 Introduction. 7.2 Limitations in the Regulatory In Vitro Genotoxicity
Tests. 7.3 Practical Issues for Genotoxicity Profiling. 7.4 Computational
Approaches to Genotoxicity Assessment: The In Silico Methods. 7.5
Genotoxicity Assays for Screening. 7.6 The "Omics". 7.7 Using Data from In
Vitro Profiling: Confirmatory Tests, Follow-Up Tests, and the Link to
Safety Assessment and In Vivo Models. 7.8 What to Test, When, and How. 7.9
Changes to Regulatory Guidelines Can Influence Screening Strategy. 7.10
Summary. 8 Hepatic Toxicity (Jinghai James Xu and Keith Hoffmaster). 8.1
Introduction. 8.2 Mechanisms of DILI. 8.3 Assays and Test Systems to
Measure Various Types of DILI. 8.4 Medicinal Chemistry Strategies to
Minimize DILI. 8.5 Future Outlooks. 9 In Vivo Toxicological Considerations
(John P. Devine, Jr). 9.1 Introduction. 9.2 Route of Administration. 9.3
Formulation Issues. 9.4 Compound Requirements. 9.5 Animal Models. 9.6
IND-Supporting Toxicology Studies. 9.7 Study Result Interpretation. 9.8
Genetic Toxicology Studies. 9.9 Conclusion. 10 Preclinical Candidate
Nomination and Development (Nils Bergenhem). 10.1 Introduction. 10.2
Investigational New Drug Application and Clinical Development. 10.3
Strategic Goals for the Preclinical Development. 10.4 Selection of
Preclinical Development Candidate. 10.5 CMC. 10.6 Preclinical Studies. 10.7
Conclusions. 11 Fragment-Based Drug Design: Considerations for Good ADME
Properties (Haitao Ji). 11.1 Introduction. 11.2 Fragment-Based Screening.
11.3 Case Studies of Fragment-Based Screening for Better Bioavailability.
11.4 De Novo Design. 11.5 Case Studies of De Novo Design for Better
Bioavailability. 11.6 Minimal Pharmacophoric Elements and Fragment Hopping.
11.7 Conclusions and Future Perspectives. Acknowledgments. References.
Index.