New Horizons in Predictive Drug Metabolism and Pharmacokinetics

Alan G E Wilson

• Publisher: Royal Society of Chemistry
• Year: 2015
• Edition: 1
• eBook ISBN:
  9781782622376
• Topic: Medicine
• Subtopic: Pharmacology

Drug metabolism, pharmacokinetics and toxicokinetics as determinants of drug attrition and the safety of xenobiotics are critically important. This book presents a comprehensive treatise on the current issues and challenges facing drug metabolism and pharmacokinetics. Readers will find a thorough exploration of their predictive role in impacting drug discovery and development and in improving the success rate and safety assessment of pharmaceuticals and industrial or occupational chemicals. Chapters not only focus on the current state of art, with distinct examples, but on future needs and approaches likely to improve our prediction of potential human risk.
Discussions of critical properties that are determinants of a compound's metabolic and pharmacokinetic fate follow introductory chapters. The Drug Discovery process increasingly incorporates pharmacokinetics and drug metabolism screening and focus has shifted towards in silico, computational and systems biology approaches. Core chapters reflect this and the recent interest and need to assess the role of transporters, along with drug metabolizing enzymes, as potential determinants of pharmacokinetic behaviour, toxicity and drug-drug interactions. Lastly, chapters cover the issues and factors involved in translating pharmacokinetics from in silico to in vivo and from animal models to man, and postulate future directions and opportunities.
Leading experts from academia, industry and regulatory bodies across the globe contribute their knowledge to this book, which scientists involved in many aspects of the drug discovery process, as well as regulators and postgraduate students, will find a useful resource.

Table of 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
• Chapter 2 - Role of Solubility, Permeability and Absorption in Drug Discovery and Development
• Chapter 3 - Models for Nonspecific Binding and Partitioning
• Chapter 4 - Cytochrome P450 Mediated Drug Metabolism
• Chapter 5 - Non-Cytochrome P450 Enzymes and Glucuronidation
• Chapter 6 - Metabolite Profiling
• Chapter 7 - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs
• Chapter 8 - Stem Cells and Drug Metabolism
• Chapter 9 - Chemically Reactive Versus Stable Drug Metabolites: Role in Adverse Drug Reactions
• Chapter 10 - Integrating Metabolism and Toxicity Properties
• Chapter 11 - Metabolomics-Based Approaches to Determine Drug Metabolite Profiles
• Chapter 12 - Drug–Drug Interactions: Regulatory and Theoretical Considerations, and an Industry Perspective
• Chapter 13 - Drug–Drug Interactions: Computational Approaches
• Chapter 14 - Induction of Hepatic Cytochrome P450 Enzymes: Importance in Drug Development and Toxicity
• Chapter 15 - Current Status and Implications of Transporters: QSAR Analysis Method to Evaluate Drug–Drug Interactions of Human Bile Salt Export Pump (ABCB11/BSEP) and Prediction of Intrahepatic Cholestasis Risk
• Chapter 16 - Formulation for Optimizing Bioavailability
• Chapter 17 - Systems Pharmacology Modeling
• Chapter 18 - Pharmacokinetic–Pharmacodynamic Modeling in Drug Development with Special Reference to Oncology
• Subject Index