Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations
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More About This Title Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations

English

With its clear, straightforward presentation, this text enables you to grasp all the fundamental concepts of pharmacokinetics and pharmacodynamics. This will allow you to understand the time course of drug response and dosing regimen design. Clinical models for concentration and response are described and built from the basic concepts presented in earlier chapters. Your understanding of the material will be enhanced by guided computer exercises conducted on a companion website. Simulations will allow you to visualize drug behavior, experiment with different dosing regimens, and observe the influence of patient characteristics and model parameters. This makes the book ideal for self-study.

By including clinical models of agonism, indirect drug effects, tolerance, signal transduction, and disease progression, author Sara Rosenbaum has created a work that stands out among introductory-level textbooks in this area.You'll find several features throughout the text to help you better understand and apply key concepts:

Three fictitious drugs are used throughout the text to progressively illustrate the development and application of pharmacokinetic and pharmacodynamic principles

Exercises at the end of each chapter reinforce the concepts and provide the opportunity to perform and solve common dosing problems

Detailed instructions let you create custom Excel worksheets to perform simple pharmacokinetic analyses

Because this is an introductory textbook, the material is presented as simply as possible. As a result, you'll find it easy to gain an accurate, working knowledge of all the core principles, apply them to optimize dosing regimens, and evaluate the clinical pharmacokinetic and pharmacodynamic literature.

English

Sara E. Rosenbaum, PhD, is Professor of Biomedical and Pharmaceutical Sciences at the University of Rhode Island, where she teaches courses in pharmacokinetics. She is also the former editor-in-chief of Clinical Research and Regulatory Affairs. Dr. Rosenbaum's research interests concentrate on the development and application of pharmacokinetic and pharmacodynamic models that build our understanding of the drug dose-response relationship.

English

Preface.

1. Introduction to Pharmacokinetics and Pharmacodynamics.

1.1 Introduction: Drugs and Doses.

1.2 Introduction to Pharmacodynamics.

1.3 Introduction to Pharmacokinetics.

1.4 Dose-Response Relationships.

1.5 Therapeutic Range.

1.6 Summary.

2. Passage of Drugs Through Membranes.

2.1 Introduction.

2.2 Structure and Properties of Membranes.

2.3 Passive Diffusion.

2.4 Carrier-Mediated Processes: Transport Proteins.

3. Drug Administration, Absorption, and Bioavailability.

3.1 Introduction: Local and Systemic Drug Administration.

3.2 Common Routes of Systemic Drug Administration.

3.3 Overview of Oral Absorption.

3.4 Extent of Drug Absorption.

3.5 Determinants of the Bioavailability.

3.6 Factors Controlling the Rate of Drug Absorption.

3.7 Biopharmaceutics Classification System.

Problems.

References. 

4. Drug Distribution.

4.1 Introduction.

4.2 Extent of Drug Distribution.

4.3 Rate of Drug Distribution.

4.4 Distribution of Drugs to the Central Nervous System.

Problems.

References.

5. Drug Elimination and Clearance.

5.1 Introduction.

5.2 Clearance.

5.3 Renal Clearance.

5.4 Hepatic Clearance.

5.5 Measurement of Clearances.

Problems.

References. 

6. Compartmental Models in Pharmacokinetics.

6.1 Introduction.

6.2 Expressions for Component Parts of the Dose-Plasma.

6.3 Putting Everything Together: Compartments and Models.

6.4 Examples of Complete Compartment Models.

6.5 Use of Compartmental Models to Study Metabolite Pharmacokinetics.

6.6 Selecting and Applying Models.

Problems.

Recommended Reading. 

7. Pharmacokinetics of an Intravenous Bolus Injection in a One-Compartment Model.

7.1 Introduction.

7.2 One-Compartment Model.

7.3 Pharmacokinetic Equations.

7.4 Simulation Exercise.

7.5 Application of the Model.

7.6 Determination of Pharmacokinetic Parameters Experimentally.

7.7 Pharmacokinetic Analysis in Clinical Practice.

Problems.

Recommended Reading. 

8. Pharmacokinetics of an Intravenous Bolus Injection in a Two-Compartment Model.

8.1 Introduction.

8.2 Tissue and Compartment Distribution of a Drug.

8.3 Basic Equation.

8.4 Relationship Between Macro and Micro Rate Constants.

8.5 Primary Pharmacokinetic Parameters.

8.6 Simulation Exercise.

8.7 Determination of the Pharmacokinetic Parameters of the Two-Compartment Model.

8.8 Clinical Application of the Two-Compartment Model.

Problems.

Recommended Reading. 

9. Pharmacokinetics of Extravascular Drug Administration.

9.1 Introduction.

9.2 Model for First-Order Absorption in a One-Compartment Model.

9.3 Bioavailability.

9.4 Simulation Exercise.

Problems.

Recommended Reading. 

10. Introduction to Noncompartmental Analysis.

10.1 Introduction.

10.2 Mean Residence Time.

10.3 Determination of Other Important Pharmacokinetic Parameters.

10.4 Different Routes of Administration.

10.5 Application of Noncompartmental Analysis to Clinical Studies.

Problems. 

11. Pharmacokinetics of Intravenous Infusion in a One-Compartment Model.

11.1 Introduction.

11.2 Model and Equations.

11.3 Steady-State Plasma Concentration.

11.4 Loading Dose.

11.5 Termination of Infusion.

11.6 Individualization of Dosing Regimens.

Problems. 

12. Multiple Intravenous Bolus Injections in the One-Compartment Model.

12.1 Introduction.

12.2 Terms and Symbols Used in Multiple-Dosing Equations.

12.3 Monoexponential Decay During a Dosing Interval.

12.4 Basic Pharmacokinetic Equations for Multiple Doses.

12.5 Steady State.

12.6 Basic Formula Revisited.

12.7 Pharmacokinetic-Guided Dosing Regimen Design.

12.8 Simulation Exercise.

Problems.

References. 

13. Multiple Intermittent Infusions.

13.1 Introduction.

13.2 Steady-State Equations for Multiple Intermittent.

13.3 Monoexponential Decay During a Dosing Interval: Dtermination of Peaks, Troughs, and Elimination Half-Life.

13.4 Determination of the Volume of Distribution.

13.5 Individualization of Dosing Regimens.

13.6 Simulation Exercise.

Problems. 

14. Multiple Oral Doses.

14.1 Introduction.

14.2 Steady-State Equations.

14.3 Equations Used Clinically to Individualize Oral Doses.

14.4 Simulation Exercise.

Problems. 

15. Nonlinear Pharmacokinetics.

15.1 Linear Pharmacokinetics.

15.2 Nonlinear Processes in Absorption, Distribution, Metabolism, and Elimination.

15.3 Pharmacokinetics of Capacity-Limited Metabolism.

15.4 Phenytoin.

Problems.

References. 

16. Introduction to Pharmacodynamic Models and Integrated Pharmacokinetic-Pharmacodynamic Models.

16.1 Introduction.

16.2 Classic Pharmacodynamic Models Based on Traditional Receptor Theory.

16.3 Empirical Pharmacodynamic Models Used Clinically.

16.4 Integrated PK-PD Models: Emax Models Combined with a PK Model for Intravenous Bolus Infection in a One-Compartment Model.

16.5 Hystersis and the Effect Compartment.

Problems.

References. 

17. Mechanism-Based Integrated Pharmacokinetic-Pharmacodynamic Models.

17.1 Introduction.

17.2 Alternative Models for Drug-Receptor Interaction: Operational Model of Agonism.

17.3 Physiological Turnover Model and Its Characteristics.

17.4 Indirect Effect Models.

17.5 Transduction and Transit Compartment Models.

17.6 Tolerance Models.

17.7 Irreversible Drug Effects.

17.8 Disease Progression Models.

Problems.

References. 

Appendix A. Review of Exponents and Logarithms.

Appendix B. Rates of Processes.

Appendix C. Creation of Excel Worksheets for Pharmacokinetic Analysis.

Appendix D. Derivation of Equations for Multiple Intravenous Bolus Injections.

Appendix E. Summary of the Properties of the Fictitious Drugs Used in the Text.

Appendix F. Computer Simulation Models.

Glossary of Abbreviations and Symbols.

Index.  

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“I could recommend Rosenbaum’s book for pharmacology students because it is written from  a perspective of drug action . . . Overall, this is a well-written introduction to PK/PD that may fill a small niche in a well-served market. “  (British Toxicology Society Newsletter, 1 June 2012)

"In summary, I believe that this book is successful in what it sets out to do. For those readers who are interested in getting to grips with the basics of the time course of onset, offset and extent of drug effects then this is the book for you. I am certainly recommending this book for my graduate students." (British Journal of Clinical Pharmacology, 2011)

"A readable font size, good quality paper and a stout binding make this an excellent offering ... This is an ideal textbook for those starting out on the pharmacokinetic trail and also for use as a reference book for those who delve occasionally into this subject." (International Society for the Study of Xenobiotics, 1 April 2012)

"In short, this is a thorough and well-designed presentation and development of key concepts in pharmacokinetics and pharmacodynamics. It is a very useful textbook, and one that I would be comfortable using in both medical and graduate teaching." (Doody's, 21 October 2011)

"Unlike other basic textbooks that cover only pharmacokinetics, the author has done justice to the title of the book by covering pharmacodynamics. Pharmacodynamics is covered in greater depth than other books in the same category. What makes the book to stand out is that the author has nicely blended the concepts of receptor theory from classical pharmacology with the modern science of PK/PD.... The book truly helps readers to understand the science of pharmacokinetics and drug action. The Excel-based simulation exercises incorporated into the text helps the reader to put his/her learning into practice, albeit in a virtual environment.... The book is strongly recommended for use in undergraduate studies of PK/PD, and by those in drug research interested in having a basic understanding of the science of PK/PD."
Ene Ette, PhD, Anoixis Corporation

"Sara Rosenbaum's book is a thoroughly modern approach to pharmacokinetics and pharmacodynamics. It is well written and well thought out – a blend of pharmacokinetic-pharmacodynamic theory and modeling/analysis concepts. The pharmacodynamic models are up to date with recent advances in the field, such as tolerance, indirect, and basic disease progression models, being presented. The web page simulations were fun to play around with allowing the user to change the model parameters and see how the results change. Rather than being a dry subject with just endless equations, the connection between the web-based simulations and the book allows the reader to be engaged and understand the subject with greater ease."
Peter L. Bonate, PhD, author of Pharmacokinetic-Pharmacodynamic Modeling and Simulation

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