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…mehr
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
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.
Inhaltsangabe
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
