New horizons in predictive drug metabolism and pharmacokinetic / edited by Alan G. E. Wilson.

Format:

Book

Author/Creator:

Alan G E Wilson

Contributor:

Wilson, Alan G. E., editor.

Royal Society of Chemistry (Great Britain), issuing body.

Series:

RSC drug discovery series ; Number 49.

RSC Drug Discovery Series, 2041-3203 ; Number 49

Language:

English

Subjects (All):

Drugs--Metabolism.

Drugs.

Pharmacokinetics.

Physical Description:

1 online resource (444 p.)

Place of Publication:

Cambridge, England : Royal Society of Chemistry, 2016.

Language Note:

English

Summary:

This book thoroughly explores the predictive role of drug metabolism and pharmacokinetics in drug discovery and in improving success rates and safety assessments of chemicals.

Contents:

Cover; New Horizons in Predictive Drug Metabolism and Pharmacokinetics; Foreword; Preface; Acknowledgements; Contents; Chapter 1 - How Physicochemical Properties of Drugs Affect Their Metabolism and Clearance; 1.1 Introduction; 1.2 Intestinal Absorption, Liver Disposition and Enzyme Expression; 1.3 Metabolic Capacity of the Intestine and Liver; 1.4 Pharmacogenomics; 1.5 Molecular Features of Importance for Transporter Interactions: Substrates Versus Inhibitors; 1.5.1 Efflux Proteins; 1.5.1.1 P-gp Substrate Recognition Pattern

1.5.1.2 Inhibition of P-gp, BCRP, MRPs, BSEP: Specificity and Overlap1.5.2 Uptake Transporters; 1.5.2.1 Inhibition of OATP1B1, OATP1B3, OATP2B1: Specificity and Overlap; 1.5.2.2 Inhibition of OCT1; 1.6 Molecular Features of Importance for Enzyme Interactions: Substrates Versus Inhibitors; 1.6.1 CYP3A4; 1.6.2 CYP2C9, CYP2C19 and CYP2D6; 1.7 Software; 1.7.1 MetaSite; 1.7.2 SMARTCyp and StarDrop; 1.8 Conclusion; Acknowledgements; References; Chapter 2 - Role of Solubility, Permeability and Absorption in Drug Discovery and Development; 2.1 Solubility; 2.1.1 Introduction

2.1.2 Methodology for Measuring Solubility2.1.3 Approaches to Increase Solubility; 2.1.3.1 Chemical Structural Modification; 2.1.3.2 Solid State Engineering; 2.1.3.3 Solubilization Enhancement; 2.1.4 Role of Solubility in Drug Discovery; 2.1.5 Role of Solubility in Drug Development; 2.2 Permeability; 2.2.1 Introduction; 2.2.2 Methodology for Measuring Permeability; 2.2.2.1 Intestinal Models; 2.2.2.2 Perfused Intestinal Segment; 2.2.2.3 Intestinal Mucosa Mounted on Ussing Chambers; 2.2.2.4 Artificial Membranes; 2.2.2.5 Cell-Based Permeability Assays

2.2.3 Applications of Cell-Based Models in Drug Discovery2.2.3.1 Absorption Prediction and BCS; 2.2.3.2 DDI Studies; 2.3 Absorption; 2.4 Closing Remarks; References; Chapter 3 - Models for Nonspecific Binding and Partitioning; 3.1 Introduction; 3.2 Models for Plasma Protein Binding; 3.2.1 HSA Models; 3.3 Models for Microsomal Membrane Partitioning; 3.4 Models for Partitioning into Hepatocytes; 3.5 pH Partitioning; 3.6 Integrated Models for Predicting VD; 3.7 Conclusion; References; Chapter 4 - Cytochrome P450 Mediated Drug Metabolism; 4.1 Function of Cytochrome P450

4.2 CYP Structures for Site of Metabolism Predictions4.2.1 Structural Differences Between the CYP Isoforms; 4.2.2 Docking and Molecular Dynamics for Site of Metabolism Predictions; 4.3 Reactivity Models for Site of Metabolism Predictions; 4.3.1 CYP-Mediated Reactions; 4.3.2 Reactivity Models for Site of Metabolism Predictions; 4.4 Perspectives; References; Chapter 5 - Non-Cytochrome P450 Enzymes and Glucuronidation; 5.1 Introduction; 5.2 FMOs; 5.2.1 Characteristics and Catalytic Mechanism; 5.2.2 Tissue Expression, Polymorphisms, and Species Differences; 5.2.3 Substrate Specificities

5.2.4 Differentiation from CYP

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

Description based on online resource; title from PDF title page (ebrary, viewed December 11, 2015).

ISBN:

9781782622376

1782622373