DescriptionThis is an authoritative, comprehensive book on the fate of drug molecules in the body, including implications for pharmacological and clinical effects. The text provides a unique, balanced approach, examining the specific physical and biological factors affecting the absorption, distribution, metabolism and excretion of drugs, together with mathematical assessment of the concentrations in plasma and body fluids. Understanding the equations requires little more than a basic knowledge of algebra, laws of indices and logarithms, and very simple calculus. A companion web site contains additional illustrations, further equations and numerous worked examples.
Whilst this book has its roots in the highly acclaimed book of the same name, written by Stephen Curry nearly thirty years ago, it is essentially a new book having been restructured and largely rewritten. This readable and informative book is an invaluable resource for professionals and students needing to develop a rational approach to the investigation and application of drugs.
About the Authors.
1 Chemical Introduction: Sources, Classification and Chemical Properties of Drugs.
1.2 Drug nomenclature and classification.
1.3 Properties of molecules.
1.4 Physicochemical interactions between drugs and other chemicals.
1.5 Law of mass action.
1.7 Partition coefficients.
2 Drug Administration and Distribution.
2.2 Drug transfer across biological membranes.
2.3 Drug administration.
2.4 Drug distribution.
2.5 Plasma protein binding.
3 Drug Elimination.
4 Elementary Pharmacokinetics.
4.2 Single-compartment models.
4.3 Non-linear kinetics.
4.4 Relationship between dose, onset and duration of effect.
4.5 Limitations of single-compartment models.
5 More Complex and Model Independent Pharmacokinetic Models.
5.2 Multiple compartment models.
5.3 Curve fitting and choice of most appropriate model.
5.4 Model independent approaches.
5.5 Population pharmacokinetics.
6 Kinetics of Metabolism and Excretion.
6.2 Metabolite kinetics.
6.3 Renal excretion.
6.4 Excretion infaeces.
7 Further Consideration of Clearance, and Physiological Modelling.
7.2 Clearance in vitro (metabolic stability).
7.3 Clearance in vivo.
7.4 Hepatic intrinsic clearance.
7.5 In vitro to in vivo extrapolation.
7.6 Limiting values of clearance.
7.7 Safe and effective use of clearance.
7.8 Physiological modelling.
7.8.1 Practical considerations.
7.9 Inhomogeneity of plasma.
8 Drug Formulation: Bioavailability, Bioequivalence and Controlled-Release Preparations.
8.3 Systemic availability.
8.4 Formulation factors affecting bioavailability.
8.6 Controlled-release preparations.
9 Factors Affecting Plasma Concentrations.
9.2 Time of administration of dose.
9.3 Food, diet and nutrition.
9.5 Circadian rhythms.
9.6 Weight and obesity.
9.9 Ambulation, posture and exercise.
10 Pharmacogenetics and Pharmacogenomics.
10.2 Methods for the study of pharmacogenetics.
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.
10.10 Pharmacodynamic differences.
11 Developmental Pharmacology and Age-related Phenomena.
11.2 Scientific and regulatory environment in regard to younger and older patients.
11.4 Physiological and pharmacokinetic processes.
11.5 Body surface area versus weight.
11.6 Age groups.
11.7 Further examples.
12 Effects of Disease on Drug Disposition.
12.2 Gastrointestinal disorders and drug absorption.
12.3 Congestive heart failure.
12.4 Liver disease.
12.5 Renal impairment.
12.6 Thyroid disease.
13 Quantitative Pharmacological Relationships.
13.2 Concentration–effect relationships (dose–response curves).
13.3 The importance of relating dose–effect and time-action studies.
14 Pharmacokinetic/Pharmacodynamic Modelling: Simultaneous Measurement of Concentrations and Effect.
14.2 PK/PD modelling.
15 Extrapolation from Animals to Human Beings and Translational Science.
15.2 Allometric scaling.
15.3 Dose-ranging versus microdosing studies.
15.4 Statistical approaches.
15.5 Translational science.
References and further reading.
16 Peptides and Other Biological Molecules.
16.2 Chemical principles.
16.3 Assay methods.
16.4 Pharmacokinetic processes.
16.5 Plasma kinetics and pharmacodynamics.
16.6 Examples of particular interest.
17 Drug Interactions.
17.3 Time action considerations.
17.4 Interactions involving drug distribution and metabolism.
17.5 Extent of drug interactions.
17.6 Key examples.
17.7 Further examples and mechanisms of a wide range of drug interactions.
17.8 When are drug interactions important?
17.9 Desirable drug–drug interactions.
17.10 Predicting the risk of future drug interactions with new chemical entities.
18 Drug Metabolism and Pharmacokinetics in Toxicology.
18.3 Dose–response and time–action with special reference to toxicology.
18.4 Safety studies in new drug discovery.
19 Drug Monitoring in Therapeutics.
19.2 General considerations.
19.3 Specific Examples.
19.4 Dose adjustment.
Appendix: Mathematical Concepts and the Trapezoidal Method.
1 Algebra, variables and equations.
2 Indices and powers.
5 Calculating AUC values: the trapezoidal method.
"Although there are numerous books on pharmacokinetics, the broad scope and thorough coverage of this one make it an excellent choice, either for a formal class or for self-study.
Each topic is carefully presented, from the simplest starting point through increasing levels of complexity.
The text provides a unique, balanced approach, examining the specific physical and biological factors affecting the absorption, distribution, metabolism and excretion of drugs, together with mathematical assessment of the concentrations in plasma and body fluids.
This readable and informative book is an invaluable resource for professionals and students needing to develop a rational approach to the investigation and application of drugs.
The broad scope of this book is intended to support its use by undergraduate, graduate, and professional students new to the field, but also by even experienced biomedical scientists and healthcare professionals as a refresher and reference. These are ambitious goals. The breadth and depth of the treatment of disposition and pharmacokinetics clearly meets the latter goal.
All the above quotes are from (Doody’s, 28 October 2012)
"The book provides a good breadth of knowledge, and readers will not be overwhelmed by unnecessary detail. For example, complex scientific and mathematical models are conveyed in a remarkably understandable manner that underpin the relevant topic rather than distracts from it. Nineteen chapters are presented in a logical sequence, each with a consistent structure and a number of different subheadings. Up-to-date and relevant references are offered at the end of each chapter, and there is a comprehensive index that is sufficiently detailed to allow readers to easily locate subject topics or worked examples . . .I would have found this book invaluable at an earlier stage of my own career, and consider it to be highly relevant to those engaged in research in either a pharmaceutical industry or academic setting. Drug Disposition and Pharmacokinetics will appeal to students from a range of scientific disciplines including medicine, toxicology, pharmacology and pharmacy. Whilst it is primarily suited to those at a postgraduate or post-doctoral level, it will also be of interest to undergraduates seeking a deeper knowledge than offered by less authoritative compact textbooks." (The British Toxicology Society, 1 May 2011)
"This is an authoritative, comprehensive book on the fate of drug molecules in the body, including implications for pharmacological and clinical effects". (HPC Market Watch, 19 January 2011)