Optimizing the "Drug-Like" Properties of Leads in Drug Discovery (eBook)

Ronald Borchardt, Edward Kerns, Michael Hageman, Dhrien Thakker, James Stevens (Herausgeber)

eBook Download: PDF

2007 | 2006
X, 512 Seiten
Springer New York (Verlag)
978-0-387-44961-6 (ISBN)

Infos

This book arises from a workshop organized by the American Association of Pharmaceutical Scientists entitled 'Optimizing the Drug-Like Properties of Leads in Drug Discovery,' which took place in Parsippany, NJ in September 2004. The workshop focused on the optimization of the drug-like properties of leads in drug discovery. The volume outlines strategies and methodologies designed to guide pharmaceutical and biotechnology companies through the drug discovery and development process.

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Drug discovery and development is a very complex, costly, and ti- consuming process. Because of the uncertainties associated with predicting the pharmacological effects and the toxicity characteristics of new chemical entities in man, their clinical development is quite prone to failure. In recent years, phar- ceutical companies have come under increasing pressure to introduce new blockbuster drugs into the marketplace more rapidly. Companies have responded to these pressures by introducing new technologies and new strategies to expedite drug discovery and development. Drug discovery and development have traditionally been divided into three separate processes (i. e. , discovery research, preclinical development, and clinical development) that ideally should be integrated both organizationally and functionally. Instead, separate and distinct discovery research, preclinical development, and clinical development divisions were created within many companies during the 1980s and 1990s, Because of their isolation, scientists in the discovery research divisions often were advancing drug candidates into preclinical development that had marginal drug-like properties. For the purpose of this presentation, "e;drug-like"e; properties refer to the molecule's physicochemical, absorption-distribution-metabolism-excretion (ADME), and toxicological properties. Lacking optimal drug-like properties often caused these drug candidates to fail in preclinical or clinical development.

Inhalt

Preface 6
Contents 9
Strategic Use of Preclinical Pharmacokinetic Studies and In Vitro Models in Optimizing ADME Properties of Lead Compounds 11
Role of Mechanistic Transport Studies in Lead Optimization 35
Metabolic Activation-Role inToxicity and Idiosyncratic Reactions 59
Case History – Use of ADME Studies for Optimization of Drug Candidates 91
Solubility, Solubilization and Dissolution in Drug Delivery During Lead Optimization 109
Lipid-based Systems, Drug Exposure and Lead Optimization 141
Biopharmaceutics Modeling and the Role of Dose and Formulation on Oral Exposure 161
Application of Physicochemical Data to Support Lead Optimization by Discovery Teams 177
Computational Models Supporting Lead Optimization in Drug Discovery 205
Prodrug Strategies for Improving Drug-Like Properties 231
The Application of Multivariate Data Analysis to Compound Property Optimization 253
Case History:Toxicology Biomarker Development Using Toxicogenomics 265
Predicting Idiosyncratic Drug Reactions 281
Elementary Predictive Toxicology for Advanced Applications 311
The Application of PK/PD Modeling and Simulations During Lead Optimization 333
Early Preclinical Evaluation of Brain Exposure in Support of Hit Identification and Lead Optimization 365
Optimizing Biomarker Development for Clinical Studies at the Lead Optimization Stage of Drug Development 421
The Relevance of Transportersin Determining Drug Disposition 433
Index 471

Produkt-Details

• Erscheint lt. Verlag: 31.12.2007
• Reihe/Serie: Biotechnology: Pharmaceutical Aspects
• Reihe/Serie: Biotechnology: Pharmaceutical Aspects
• Zusatzinfo: X, 512 p. 190 illus., 39 illus. in color.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitsfachberufe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Medizin / Pharmazie ► Pharmazie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: Borchardt • Discovery • Drug • lead • Leads • Like • Optimizing • Properties
• ISBN-10: 0-387-44961-2 / 0387449612
• ISBN-13: 978-0-387-44961-6 / 9780387449616