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Home Basic Pharmacokinetics and Pharmacodynamics

Basic Pharmacokinetics and Pharmacodynamics

An Integrated Textbook and Computer Simulations

Sara E. Rosenbaum
Klinische farmacologie, farmacotherapie, Fundamentele farmacologie, Farmaceutische wetenschappen, Farmacie
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  • Basic Pharmacokinetics and Pharmacodynamics - 9781119143154
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Updated with new chapters and topics, this book provides a comprehensive description of all essential topics in contemporary pharmacokinetics and pharmacodynamics. It also features interactive computer simulations for students to experiment and observe PK/PD models in action.

•    Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner
•    Helps students better appreciate important concepts and gain a greater understanding of the mechanism of action of drugs by reinforcing practical applications in both the book and the computer modules
•    Features interactive computer simulations, available online through a companion website at: http://www.uri.edu/pharmacy/faculty/rosenbaum/basicmodels.html•    Adds new chapters on physiologically based pharmacokinetic models, predicting drug-drug interactions,  and pharmacogenetics while also strengthening original chapters to better prepare students for more advanced applications
•    Reviews of the 1st edition: “This is an ideal textbook for those starting out … and also for use as a reference book …." (International Society for the Study of Xenobiotics) and “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 …. “  (British Toxicology Society Newsletter)

Contents

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 AND DRUG ABSORPTION
Steven Sutton

3.1 Introduction: Local and Systemic Drug Administration

3.2 Routes of Drug Administration

3.3 Overview of Oral Absorption

3.4 Extent of Drug Absorption

3.5 Determinants of the Fraction of the Dose Absorbed (F)

3.6 Factors Controlling the Rate of Drug Absorption

3.7 Biopharmaceutics Classification System

3.8 Food effects

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 Elimination and Clearance

Problems

References

6. COMPARTMENTAL MODELS IN PHARMACOKINETICS

6.1 Introduction

6.2 Expressions for Component Parts of the Dose–Plasma Concentration Relationship

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

8. PHARMACOKINETICS OF AN INTRAVENOUS BOLUS INJECTION IN A TWO-COMPARTMENT MODEL

8.1 Introduction

8.2 Tissue and Compartmental 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

9. PHARMACOKINETICS OF EXTRAVASCULAR DRUG ADMINISTRATION
Steven Sutton

9.1 Introduction

9.2 First-Order Absorption in a One-Compartment Model

9.3 Modified Release and Gastric Retention Formulation

9.4 Bioavailability

9.5 In Vitro-In Vivo Correlation (IVIVC)

9.6 Simulation Exercise

Problems

References

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

13. MULTIPLE INTERMITTENT INFUSIONS

13.1 Introduction

13.2 Steady-State Equations for Multiple Intermittent Infusions

13.3 Monoexponential Decay During a Dosing Interval: Determination 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

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

16. INTRODUCTION TO PHARMACOGENETICS

16.1 Introduction

16.2 Genetics Primer

16.3 Pharmacogenetics

16.4 Genetics and Pharmacodynamics

16.5 Summary

Reference and Recommended Reading

17. MODELS USED TO PREDICT DRUG-DRUG INTERACTIONS FOR ORALLY ADMINISTERED DRUGS

17.1 Introduction

17.2 Mathematical Models For In Vitro Data on Inhibitors and Inducers of Drug Metabolism

17. 3. Surrogate In Vivo Values For the Unbound Concentration of the Perpetrator at the Site of Action

17.4. Model To Predict DDIs In Vivo

17.5. Predictive Models For Transporter-Based DDIs

17.6. Application of Physiologically Based Modeling to DDI Prediction: the Dynamic Approach

17.7. Conclusion

Problems

References

18. INTRODUCTION TO PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING

18.1 Introduction

18.2 Components of PBPK Models

18.3 Equations of PBPK Models

18.4 Building a Model

18.5 Simulations

18.6 Estimation of Drug Specific Parameters

18.7 More Detailed PBPK Models

18.8 Application of PBPK Models

Reference

19. INTRODUCTION TO PHARMACODYNAMIC MODELS AND INTEGRATED PHARMACOKINETIC–PHARMACODYNAMIC MODELS
Diane Mould and Paul Hutson

19.1 Introduction

19.2 Classic Pharmacodynamic Models Based On Receptor Theory

19.3 Direct Effect Pharmacodynamic Models

19.4 Integrated Pk–Pd Models: Intravenous Bolus Injection In The One-Compartment Mode And The Sigmoidal Emax Model

19.5 Pharmacodynamic Drug-Interactions

PROBLEMS

REFERENCES

20. SEMI-MECHANISTIC PHARMACOKINETIC–PHARMACODYNAMIC MODEL
Diane Mould and Paul Hutson

20.1 Introduction

20.2 Hysteresis and the Effect Compartment

20.3 Physiological Turnover Models and Their Characteristics

20.4 Indirect Effect Models

20.5 Other Indirect Effect Models

20.6 Models Of Tolerance

20.7 Irreversible Drug Effects

20.8 Disease Progression Models

Problems

References

APPENDIX A REVIEW OF EXPONENTS AND LOGARITHMS

A.1 Exponents

A.2 Logarithms: log and ln

A.3 Performing Calculations in the Logarithmic Domain

A.4 Calculations Using Exponential Expressions and Logarithms

A.5 Decay Function: e−kt

A.6 Growth Function: 1 − e−kt

A.7 Decay Function in Pharmacokinetics

Problems

APPENDIX B. RATES OF PROCESSES

B.1 Introduction

B.2 Order of a Rate Process

B.3 Zero-Order Processes

B.4 First-Order Processes

B.5 Comparison of Zero- and First-Order Processes

B.6 Detailed Example of First-Order Decay in Pharmacokinetics

B.7 Examples of the Application of First-Order Kinetics to Pharmacokinetics

APPENDIX C. CREATION OF EXCEL WORKSHEETS FOR PHARMACOKINETIC ANALYSIS

C.1 Measurement of AUC and Clearance

C.2 Analysis of Data from an Intravenous Bolus Injection in a One-Compartment Model

C.3 Analysis of Data from an Intravenous Bolus Injection in a Two-Compartment Model

C.4 Analysis of Oral Data in a One-Compartment Model

C.5 Noncompartmental Analysis of Oral Data

APPENDIX D. DERIVATION OF EQUATIONS FOR MULTIPLE INTRAVENOUS BOLUS INJECTIONS

D.1 Assumptions

D.2 Basic Equation for Plasma Concentration After Multiple Intravenous Bolus Injections

D.3 Steady-State Equations

APPENDIX E ENZYME KINETICS: MICHAELIS MENTEN EQUATION. AND MODELS FOR INHIBITORS AND INDUCERS OF DRUG METABOLISM

E.1 KINETIC OF DRUG METABOLISM: THE MICHAELIS MENTEN MODEL

E.2. Effect of Perpetrators of DDIs on Enzyme Kinetics and Intrinsic Clearance.

APPENDIX F. SUMMARY OF THE PROPERTIES OF THE FICTITIOUS DRUGS USED IN THE TEXT

APPENDIX G. COMPUTER SIMULATION MODELS

Specificaties
Uitgeverij
John Wiley & Sons Inc
Publicatiedatum
30 november 2016
Pagina's
608
ISBN
9781119143154
Editie
2
Uitvoering
Paperback
Over de auteur
Sara E. Rosenbaum, PhD, is Professor of Biomedical and Pharmaceutical Sciences at the University of Rhode Island, where she teaches courses in pharmacokinetics and pharmacodynamics. Her research interests concentrate on the development and application of pharmacokinetic and pharmacodynamic models to better understand the drug dose-response relationship.

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