Introduction to Drug Disposition and Pharmacokinetics

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