Predictive ADMET : integrative approaches in drug discovery and development / edited by Jianling Wang, Laszlo Urban ; Shirley A. Aguirre [and sixty others], contributors.

Format:

Book

Contributor:

Wang, Jianling, 1958-

Urban, Laszlo, 1951-

Aguirre, Shirley A.

Language:

English

Subjects (All):

Pharmacokinetics.

Physical Description:

1 online resource (624 p.)

Edition:

1st ed.

Place of Publication:

Hoboken, New Jersey : Wiley, 2014.

Language Note:

English

Summary:

By guiding in the application of techniques and tools for predicting ADMET outcomes in drug candidates, Predictive ADMET offers a road map for drug discovery scientists to generate effective and safe drugs for unmet medical needs. Featuring case studies and lessons learned from real drug discovery and development, the text: helps users diagnose ADMET problems; presents appropriate recommendations; introduces the current clinical practice for drug discovery and development; and consolidates the tools and models to intelligently integrate existing in silico, in vitro and in vivo ADMET dat

Contents:

Predictive ADMET; Contents; Preface; Contributors; I Introduction to the current scientific, clinical, and social environment of drug discovery and development; 1 Current Social, Clinical, and Scientific Environment of Pharmaceutical R&D; 1.1 THE CHANGING LANDSCAPE OF EPIDEMIOLOGY AND MEDICAL CARE; 1.2 COST OF DRUG DEVELOPMENT; 1.2.1 Decline in Industry Productivity; 1.2.2 Rise in Safety Issues; 1.2.3 Increasing Regulatory Requirements; 1.3 THE NEW PARADIGM OF ADMEPK ASSESSMENT; 1.3.1 Recent Advancement of ADMEPK Assessment of Drug Candidates in Discovery and Development

1.3.2 New Challenges and Emerging Fields of ADMEPK Development1.4 INCREASED SAFETY EXPECTATIONS; 1.4.1 Early Awareness of Safety Hazards; 1.4.2 Logistics for In Vitro Safety Profiling; 1.4.3 Relevance and Confidence in Profiling Data; 1.5 TRANSLATIONAL VALUE OF IN VITRO PROFILING DATA; 1.6 SUMMARY; References; 2 Polypharmacology and Adverse Bioactivity Profiles Predict Potential Toxicity and Drug-related ADRs; 2.1 INTRODUCTION; 2.2 IN VITRO ADMET PROFILING; 2.3 COMPUTATIONAL METHODS PREDICTING ADMET PROPERTIES; 2.3.1 QSAR, QSPR, and Descriptor-based Methods

2.3.2 Molecular Interaction- and Shape-based Approaches2.3.3 Docking; 2.4 OUTLOOK; Acknowledgments; References; II Intelligent integration and extrapolation of ADMET data; 3 ADMET Diagnosis Models; 3.1 Introduction; 3.2 Solubility Diagnosis; 3.2.1 Lipophilicity and Maximum Solubility Concept; 3.2.2 Estimating the Impact of the Solid State in the Absence of Crystalline Material; 3.2.3 When Is the Maximal Effect of Ionization Reached?; 3.2.4 The Solubility Diagnosis Matrix; 3.2.5 Diagnosis Examples (Molecules in Table); 3.3 Diagnosing Permeability

3.3.1 LogP, PSA, Absorption Model, and Polarity-Lipophilicity Line (PLL)3.3.2 The Permeability Diagnosis Matrix (see Table); 3.3.3 Diagnosis Examples (Molecules in Table); 3.4 General Strategy to Apply Adme Diagnosis Models; 3.5 Concluding Remarks; References; 4 PATH (Probe ADME and Test Hypotheses): A Useful Approach Enabling Hypothesis-driven ADME Optimization; 4.1 Introduction; 4.2 Assumptions and Limitations; 4.2.1 In vitro; 4.2.2 In vivo; 4.3 Clearance IVIVC; 4.3.1 Establishing a Baseline for Clearance Correlation Analysis; 4.3.2 Clearance IVIVC Zones

4.3.3 Trends, Hypotheses, and Strategies for Clearance Interrogation by Zone4.4 Oral Bioavailability (%F) IVIVC; 4.4.1 Establishing a Baseline for %F Correlation Analysis; 4.4.2 %F IVIVC Zones; 4.4.3 Trends, Hypotheses, and Strategies for %F Interrogation by Zone; 4.5 Payoffs for Intelligent Data Integration in Early Drug Discovery; References; 5 PK-MATRIX-A Permeability: Intrinsic Clearance System for Prediction, Classification, and Profiling of Pharmacokinetics and Drug-Drug Interactions; 5.1 INTRODUCTION; 5.2 SETTING UP THE PK-MATRIX; 5.3 PK-MATRIX DISTRIBUTION/CLASSIFICATION OF DRUGS

5.3.1 Pe versus Hepatic Metabolic CLint

Notes:

Description based upon print version of record.

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

1-118-78334-4

1-118-78330-1

OCLC:

858975739