Basic Pharmacokinetics and Pharmacodynamics E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1080

Veröffentlichungsjahr: 2016

Beschreibung

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: https://web.uri.edu/pharmacy/research/rosenbaum/sims/
•    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)

Leseprobe

BASIC PHARMACOKINETICSAND PHARMACODYNAMICS

An Integrated Textbook andComputer Simulations

Second Edition

Edited by

SARA E. ROSENBAUM

Copyright © 2017 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, [phone], fax [phone], or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, [phone], fax [phone], or online at http://www.wiley.com/go/permission.

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Library of Congress Cataloging-in-Publication Data:

Names: Rosenbaum, Sara (Sara E.), author, editor. Title: Basic pharmacokinetics and pharmacodynamics : an integrated textbook and computer simulations / edited  by Sara E. Rosenbaum. Description: Second edition. | Hoboken, New Jersey : John Wiley & Sons, Inc., [2017] | Includes bibliographical   references and index. Identifiers: LCCN 2016031846 (print) | LCCN 2016034126 (ebook) | ISBN 9781119143154 (pbk.) |  ISBN 9781119143161 (pdf) | ISBN 9781119143185 (epub) Subjects: | MESH: Pharmacokinetics | Pharmacological Phenomena | Computer Simulation Classification: LCC RM301.5 (print) | LCC RM301.5 (ebook) | NLM QV 38 | DDC 615/.7–dc23 LC record available at https://lccn.loc.gov/2016031846

To Steve, Molly and Lucy

CONTENTS

Preface

Contributors

Chapter 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

Reference

Chapter 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

References

Chapter 3 Drug Administration and Drug Absorption

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

Chapter 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

Note

References

Chapter 5 Drug Elimination and Clearance

5.1 Introduction

5.2 Clearance

5.3 Renal Clearance

5.4 Hepatic Elimination and Clearance

Problems

References

Chapter 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

Suggested Readings

Chapter 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

Suggested Reading

Chapter 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

Suggested Readings

Chapter 9 Pharmacokinetics of Extravascular Drug Administration

9.1 Introduction

9.2 First-Order Absorption in a One-Compartment Model

9.3 Modified Release and Gastric Retention Formulations

9.4 Bioavailability

9.5

IN VITRO-IN VIVO

Correlation

9.6 Simulation Exercise

Problems

References

Chapter 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

Chapter 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

Chapter 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

Reference

Chapter 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

Problems

Chapter 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

References

Chapter 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

Chapter 16 Introduction to Pharmacogenetics

16.1 Introduction

16.2 Genetics Primer

16.3 Pharmacogenetics

16.4 Genetics and Pharmacodynamics

16.5 Summary

Reference

Suggested Readings

Chapter 17 Models Used to Predict Drug–Drug Interactions for Orally Administered Drugs

17.1 Introduction

17.2 Mathematical Models for Inhibitors and Inducers of Drug Metabolism Based on

IN VITRO

Data

17.3 Surrogate

IN VIVO

Values for the Unbound Concentration of the Perpetrator at the site of action

17.4 Models Used to Predict DDIs

IN VIVO

17.5 Predictive Models for Transporter-Based DDIs

17.6 Application of Physiologically Based Pharmacokinetic Models to DDI Prediction: The Dynamic Approach

17.7 Conclusion

Problems

References

Chapter 18 Introduction to Physiologically Based Pharmacokinetic Modeling

18.1 Introduction

18.2 Components of PBPK Models

18.3 Equations for PBPK Models

18.4 Building a PBPK Model

18.5 Simulations

18.6 Estimation of Human Drug-Specific Parameters

18.7 More Detailed PBPK Models

18.8 Application of PBPK Models

References

Chapter 19 Introduction to Pharmacodynamic Models and Integrated Pharmacokinetic–Pharmacodynamic Models

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

E

max

Model

19.5 Pharmacodynamic Drug–Drug Interactions

Problems

References

Chapter 20 Semimechanistic Pharmacokinetic–Pharmacodynamic Models

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 Kinetics of Drug Metabolism: The Michaelis–Menten Model

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

References

Appendix F Summary of the Properties of the Fictitious Drugs used in the Text

Appendix G Computer Simulation Models

Glossary of Terms

Index

EULA

List of Tables

Chapter 1

Table 1.1

Table 1.2

Table 1.3

Chapter 2

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Chapter 3

Table 3.1

Table 3.2

Table 3.3

Table 3.4

Table 3.5

Table 3.6

Table P3.7

Chapter 4

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 4.5

Table 4.6

Table 4.7

Table P4.7

Chapter 5

Table 5.1

Table 5.2

Table 5.3

Table E5.3A

Table E5.3B

Table 5.4

Table 5.5

Table 5.6

Table 5.7

Table 5.8

Table 5.9

Table P5.11

Table P5.12

Table P5.13

Chapter 7

Table 7.1

Table 7.2

Table SE7.4

Table E7.5

Table E7.6

Table P7.8

Chapter 8

Table 8.1

Table E8.1

Table P8.4

Table P8.5

Table P8.7

Table E9.1A

Chapter 9

Table E9.1B

Table 9.1

Table P9.1

Table P9.2

Chapter 10

Table E10.1

Table E10.2A

Table E10.2B

Table E10.3A

Table E10.3B

Table P10.1

Table P10.2

Table P10.3

Chapter 11

Table SE11.1

Table 11.1

Table SE11.2

Table P11.5

Chapter 12

Table 12.1

Table 12.2

Table SE12.1

Table SE12.2

Table SE12.3

Chapter 13

Table E13.3

Table P13.4

Chapter 15

Table 15.1

Table 15.2

Chapter 16

Table 16.1

Table 16.2

Chapter 17

Table 17.1

Table 17.2

Table 17.3

Table 17.4

Chapter 18

Table 18.1

Table 18.2

Table 18.3

Chapter 20

Table 20.1

Table 20.2

Table 20.3

Table P20.1A

Table P20.1B

Table P20.2A

Table P20.2B

Table P20.3

Table P20.5

Table P20.6

Table P20.7

Appendix A

Table A.1

Table A.2

Appendix B

Table B.1

Table B.2

Appendix C

Table C.1

Table C.2

Table C.3

Table C.4

Appendix D

Table D.1

Appendix F

Table F.1