Despite increased spending on research and development, the number of new medicines marketed successfully continues to decline. The Pharmaceutical industry is therefore focussing on ways to reduce attrition by addressing frequent reasons for clinical drug failures very early in the drug discovery process. One of the biggest challenges is the pharmacokinetic (PK) optimisation of drug candidates tailored and predicted to have appropriate absorption, distribution, metabolism and excretion (ADME) characteristics in human. This book describes how traditional pbarmacokinetic approaches and methods are being re-invented' to meet specific needs dictated by the dynamics of the drug discovery process. The book gives an overview of state-of-the-art tools and their use in the decision-making process is discussed by a number of scientists from leading pharmaceutical companies.

Inhalt

1 Accelerating the Process of Drug Discovery.- 2 The Role of Pharmacokinetics in Drug Discovery: Finding Drug Candidates with the Greatest Potential for Success.- 3 Rapid Permeability Screening in Drug Discovery to Predict Human Intestinal Absorption.- 4 Drug Metabolism Assays and Their Use in Drug Discovery.- 5 Prediction of Human Pharmacokinetics Based on Preclinical In Vitro and In Vivo Data.- 6 In Vitro Screening of Cytochrome P450 Induction Potential.- 7 Drug Transport Across the Blood-Brain Barrier.- 8 The Development and Implementation of Bioanalytical Methods Using LC-MS to Support ADME Studies in Early Drug Discovery and Candidate Selection.- 9 Strategies in Lead Selection and Optimization: Application of a Graphical Model and Automated In Vitro ADME Screening.- 10 High-Throughput Screening - Brains Versus Brawn.- 11 Relation of Molecular Properties with Drug Absorption and Disposition.- 12 Modelling Human Cytochrome P450-Substrate Interactions.- 13 Forum Discussion.- Previous Volumes Published in This Series.