Introduction to Drug Disposition and Pharmacokinetics

Klappentext The application of knowledge of drug disposition, and skills in pharmacokinetics, are crucial to the development of new drugs and to a better understanding of how to achieve maximum benefit from existing ones. The book takes the reader from basic concepts to a point where those who wish to will be able to perform pharmacokinetic calculations and be ready to read more advanced texts and research papers.The book will be of benefit to students of medicine, pharmacy, pharmacology, biomedical sciences and veterinary science, including those who have elected to study the topic in more detail, such as via electives and special study modules. It will be of benefit to those involved in drug discovery and development, pharmaceutical and medicinal chemists, as well as budding toxicologists and forensic scientists who require the appropriate knowledge to interpret their findings and as an introductory text for clinical pharmacologists. Early chapters describe the basic principles of the topic while the later ones illustrate the application of those principles to modern approaches to drug development and clinical use. Full colour illustrations facilitate the learning experience and supporting material for course leaders and students can be found on the Companion Web Site Zusammenfassung The application of knowledge of drug disposition, and skills in pharmacokinetics, are crucial to the development of new drugs and to a better understanding of how to achieve maximum benefit from existing ones. The book takes the reader from basic concepts to a point where those who wish to will be able to perform pharmacokinetic calculations and be ready to read more advanced texts and research papers.The book will be of benefit to students of medicine, pharmacy, pharmacology, biomedical sciences and veterinary science, including those who have elected to study the topic in more detail, such as via electives and special study modules. It will be of benefit to those involved in drug discovery and development, pharmaceutical and medicinal chemists, as well as budding toxicologists and forensic scientists who require the appropriate knowledge to interpret their findings and as an introductory text for clinical pharmacologists. Early chapters describe the basic principles of the topic while the later ones illustrate the application of those principles to modern approaches to drug development and clinical use. Full colour illustrations facilitate the learning experience and supporting material for course leaders and students can be found on the Companion Web Site Inhaltsverzeichnis Preface ixCompanion Website Directions xii1. Introduction: Basic Concepts 11.1 Introduction 11.2 Drugs and drug nomenclature 31.3 Law of mass action 41.4 Ionization 91.5 Partition coefficients 121.6 Further reading 142. Drug Administration and Distribution 152.1 Introduction 152.2 Drug transfer across biological membranes 162.3 Drug administration 222.4 Drug distribution 312.5 Plasma protein binding 382.6 Further reading 432.7 References 433. Drug Metabolism and Excretion 453.1 Introduction 453.2 Metabolism 463.3 Excretion 583.4 Further reading 693.5 References 694. Single-compartment Pharmacokinetic Models 714.1 Introduction 724.2 Systemic clearance 744.3 Intravenous administration 764.4 Absorption 794.5 Infusions 874.6 Multiple doses 904.7 Non-linear kinetics 944.8 Relationship between dose, and onset and duration of effect 984.9 Limitations of single-compartment models 994.10 Further reading 1004.11 References 1005. Multiple-compartment and Non-compartment Pharmacokinetic Models 1025.1 Multiple-compartment models 1025.2 Non-compartmental models 1175.3 Population pharmacokinetics 1215.4 Curve fitting and the choice of most appropriate model 1225.5 Further reading 1245.6 References 1246. Kinetics of Metabolism and Excretion 1266.1 Introduction 1266.2 Me...

Autorentext

Stephen Curry was Professor of Pharmacology at The London Hospital Medical College, Professor of Pharmaceutical Sciences at the University of Florida, and Professor of Pharmacology and Physiology at the University of Rochester before founding ADispell. He also spent ten years with AstraZeneca and predecessor companies. A graduate of De Montfort University and King's College London, he was honoured by the Faculty of Medicine of London University with the award of the Doctor of Medical Science Degree and is a Fellow of the Royal Pharmaceutical Society. As CEO of ADispell, he currently works in the field of technology transfer and translational science with early stage companies based on discoveries at The University of Rochester and Cornell University.

Robin Whelpton, after obtaining his first degree in Applied Chemistry, joined the Department of Pharmacology and Therapeutics, The London Hospital Medical College, University of London as research assist to Professor Curry. Having obtained his PhD in Pharmacology, he became Lecturer and then Senior Lecturer before transferring to Queen Mary University of London to teach pharmacology to preclinical medical and dental students. His last post before retiring was Senior Lecturer in Pharmaceutical Chemistry in the School of Biological and Chemical Sciences. He has wealth of experience teaching drug distribution and pharmacokinetics to undergraduate and postgraduate students of medicine, dentistry, pharmacology, pharmacy, biomedical sciences, pharmaceutical chemistry and forensic science.

Inhalt

Preface ix Companion Website Directions xii 1. Introduction: Basic Concepts 1 1.1 Introduction 1 1.2 Drugs and drug nomenclature 3 1.3 Law of mass action 4 1.4 Ionization 9 1.5 Partition coefficients 12 1.6 Further reading 14 2. Drug Administration and Distribution 15 2.1 Introduction 15 2.2 Drug transfer across biological membranes 16 2.3 Drug administration 22 2.4 Drug distribution 31 2.5 Plasma protein binding 38 2.6 Further reading 43 2.7 References 43 3. Drug Metabolism and Excretion 45 3.1 Introduction 45 3.2 Metabolism 46 3.3 Excretion 58 3.4 Further reading 69 3.5 References 69 4. Single-compartment Pharmacokinetic Models 71 4.1 Introduction 72 4.2 Systemic clearance 74 4.3 Intravenous administration 76 4.4 Absorption 79 4.5 Infusions 87 4.6 Multiple doses 90 4.7 Non-linear kinetics 94 4.8 Relationship between dose, and onset and duration of effect 98 4.9 Limitations of single-compartment models 99 4.10 Further reading 100 4.11 References 100 5. Multiple-compartment and Non-compartment Pharmacokinetic Models 102 5.1 Multiple-compartment models 102 5.2 Non-compartmental models 117 5.3 Population pharmacokinetics 121 5.4 Curve fitting and the choice of most appropriate model 122 5.5 Further reading 124 5.6 References 124 6. Kinetics of Metabolism and Excretion 126 6.1 Introduction 126 6.2 Metabolite kinetics 127 6.3 Renal excretion 137 6.4 Excretion in faeces 142 6.5 Further reading 143 6.6 References 144 7. Clearance, Protein Binding and Physiological Modelling 145 7.1 Introduction 145 7.2 Clearance 146 7.3 Physiological modelling 158 7.4 Further reading 161 7.5 References 161 8. Quantitative Pharmacological Relationships 162 8.1 Pharmacokinetics and pharmacodynamics 162 8.2 Concentration-effect relationships (dose-response curves) 163 8.3 Time-dependent models 169 8.4 PK-PD modelling 173 8.5 Further reading 177 8.6 References 177 9. Pharmacokinetics of Large Molecules 178 9.1 Introduction 178 9.2 Pharmacokinetics 179 9.3 Plasma kinetics and pharmacodynamics 184 9.4 Examples of particular interest 185 9.5 Further reading 191 9.6 References 191 10. Pharmacogenetics and Pharmacogenomics 192 10.1 Introduction 192 10.2 Methods for the study of pharmacogenetics 193 10.3 N-Acetyltransferase 194 10.4 Plasma cholinesterase 197 10.5 Cytochrome P450 polymorphisms 199 10.6 Alcohol dehydrogenase and acetaldehyde dehydrogenase 202 10.7 Thiopurine methyltransferase 202 10.8 Phase 2 enzymes 202 10.9 Transporters 204 10.10 Ethnicity 206 10.11 Pharmacodynamic differ…