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Index
Cover
Title Page
Table of Contents
Preface
Companion Website Directions
1 Introduction
1.1 Introduction
1.2 Drugs and drug nomenclature
1.3 Law of mass action
1.4 Ionization
1.5 Partition coefficients
1.6 Further reading
2 Drug Administration and Distribution
2.1 Introduction
2.2 Drug transfer across biological membranes
2.3 Drug administration
2.4 Drug distribution
2.5 Plasma protein binding
2.6 Further reading
2.7 References
3 Drug Metabolism and Excretion
3.1 Introduction
3.2 Metabolism
3.3 Excretion
3.4 Further reading
3.5 References
4 Single-compartment Pharmacokinetic Models
4.1 Introduction
4.2 Systemic clearance
4.3 Intravenous administration
4.4 Absorption
4.5 Infusions
4.6 Multiple doses
4.7 Non-linear kinetics
4.8 Relationship between dose, and onset and duration of effect
4.9 Limitations of single-compartment models
4.10 Further reading
4.11 References
5 Multiple-compartment and Non-compartment Pharmacokinetic Models
5.1 Multiple-compartment models
5.2 Non-compartmental models
5.3 Population pharmacokinetics
5.4 Curve fitting and the choice of most appropriate model
5.5 Further reading
5.6 References
6 Kinetics of Metabolism and Excretion
6.1 Introduction
6.2 Metabolite kinetics
6.3 Renal excretion
6.4 Excretion in faeces
6.5 Further reading
6.6 References
7 Clearance, Protein Binding and Physiological Modelling
7.1 Introduction
7.2 Clearance
7.3 Physiological modelling
7.4 Further reading
7.5 References
8 Quantitative Pharmacological Relationships
8.1 Pharmacokinetics and pharmacodynamics
8.2 Concentration–effect relationships (dose–response curves)
8.3 Time-dependent models
8.4 PK-PD modelling
8.5 Further reading
8.6 References
9 Pharmacokinetics of Large Molecules
9.1 Introduction
9.2 Pharmacokinetics
9.3 Plasma kinetics and pharmacodynamics
9.4 Examples of particular interest
9.5 Further reading
9.6 References
10 Pharmacogenetics and Pharmacogenomics
10.1 Introduction
10.2 Methods for the study of pharmacogenetics
10.3 N-Acetyltransferase
10.4 Plasma cholinesterase
10.5 Cytochrome P450 polymorphisms
10.6 Alcohol dehydrogenase and acetaldehyde dehydrogenase
10.7 Thiopurine methyltransferase
10.8 Phase 2 enzymes
10.9 Transporters
10.10 Ethnicity
10.11 Pharmacodynamic differences
10.12 Personalized medicine
10.13 Further reading
10.14 References
11 Additional Factors Affecting Plasma Concentrations
11.1 Introduction
11.2 Pharmaceutical factors
11.3 Sex
11.4 Pregnancy
11.5 Weight and obesity
11.6 Food, diet and nutrition
11.7 Time of day
11.8 Posture and exercise
11.9 Further reading
11.10 References
12 Effects of Age and Disease on Drug Disposition
12.1 Introduction
12.2 Age and development
12.3 Effects of disease on drug disposition
12.4 Assessing pharmacokinetics in special populations
12.5 Further reading
12.6 References
13 Drug Interactions and Toxicity
13.1 Introduction
13.2 Drug interactions
13.3 Toxicity
13.4 Further reading
13.5 References
14 Perspectives and Prospects
14.1 Drug disposition and fate
14.2 Pharmacodynamics
14.3 Quantification of drugs and pharmacokinetics
14.4 The future
14.5 Postscript
14.6 Further reading
14.7 References
Appendix 1: Mathematical Concepts and the Trapezoidal Method
A1.1 Algebra, variables and equations
A1.2 Indices and powers
A1.3 Logarithms
A1.4 Calculus
A1.5 Calculating AUC values: the trapezoidal method
Appendix 2: Dye Models to Teach Pharmacokinetics
A2.1 Introduction to the dye model
A2.2 Arrangement for i.v. bolus or zero-order infusions
A2.3 Arrangement for first-order absorption
Appendix 3: Curve Fitting
A3.1 Graphical solution: method of residuals
A3.2 Iterative curve-fitting
A3.3 Reference
Appendix 4: Pharmacokinetic Simulations
A4.1 Simulations for Chapter 4
A4.2 Simulations for Chapter 5
A4.3 Simulations for Chapter 7
Index
End User License Agreement
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