Comparative Pharmacokinetics: Principles, Techniques, and Applications, Second Edition

442 Pages·2011·6.913 MB·English

by  Jim E. Riviere(auth.)

Comparative Pharmacokinetics
Comparative Pharmacokinetics: Principles, Techniques, and Applications, Second Edition. Jim E. Riviere.
© 2011 Jim E. Riviere. Published 2011 by John Wiley & Sons, Inc. ISBN: 978-0-813-82993-7
Comparative Pharmacokinetics
Principles, Techniques, and Applications
Second Edition
Jim E. Riviere
A John Wiley & Sons, Inc., Publication
This edition fi rst published 2011 © 2011 by Jim E. Riviere
First edition published 1999 © 1999 Iowa State University Press
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Library of Congress Cataloging-in-Publication Data
Riviere, Jim E. (Jim Edmond), author.
Comparative pharmacokinetics / Jim E. Riviere, North Carolina State University, Raleigh, North Carolina.
– 2nd Edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-8138-2993-7 (pbk. : alk. paper)
1. Pharmacokinetics. 2. Veterinary pharmacology. I. Title.
[DNLM: 1. Pharmacokinetics. QV 38]
RM301.5.R58 2011
636.089′578–dc22
2010047729
A catalogue record for this book is available from the British Library.
Set in 10/12pt Times by Toppan Best-set Premedia Limited
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1 2011
Contents
Coauthors vii
Preface ix
1 Introduction 3
2 Principles of Drug Movement in the Body 13
3 Quantitative Structure–Permeability Relationships 27
with Xin-Rui Xia
4 Absorption 39
5 Distribution 73
with Jennifer Buur
6 Renal Elimination 91
7 Hepatic Biotransformation and Biliary Excretion 113
with Ronald Baynes
8 Compartmental Models 143
9 Noncompartmental Models 187
10 Nonlinear Models 207
11 Physiological Models 225
with Teresa Leavens
12 Dosage Regimens 241
13 Simultaneous Pharmacokinetic–Pharmacodynamic Modeling 255
with Pierre-Louis Toutain
14 Study Design and Data Analysis 295
with Jason Chittenden
v
vi Contents
15 Bioequivalence Studies 315
with Marilyn Martinez
16 Population Pharmacokinetic Models 347
with Jason Chittenden
17 Dosage Adjustments in Disease States 379
with Jennifer Davis
18 Interspecies Extrapolations 399
19 Tissue Residues and Withdrawal Times 413
with Sharon Mason
Index 425
Coauthors
The numbers in parentheses indicate chapters coauthored with Dr. Jim E. Riviere.
Ronald Baynes (7) Jennifer Davis (17)
Center for Chemical Toxicology Research Department of Clinical Sciences
and Pharmacokinetics College of Veterinary Medicine
Department of Population Health and North Carolina State University
Pathobiology Raleigh, NC, USA
College of Veterinary Medicine [email protected]
North Carolina State University
Raleigh, NC, USA Teresa Leavens (11)
[email protected] Center for Chemical Toxicology Research
and Pharmacokinetics
James Brooks (Illustrator) Department of Population Health and
Center for Chemical Toxicology Research Pathobiology
and Pharmacokinetics College of Veterinary Medicine
Department of Population Health and North Carolina State University
Pathobiology Raleigh, NC, USA
College of Veterinary Medicine [email protected]
North Carolina State University
Raleigh, NC, USA Sharon Mason (19)
[email protected] Department of Biological Sciences
Campbell University
Jennifer Buur (5) Buies Creek, NC, USA
College of Veterinary Medicine [email protected]
Western University of Health Sciences
Pomona, CA, USA Marilyn Martinez (15)
[email protected] Center for Veterinary Medicine
US Food and Drug Administration
Jason Chittenden (14 and 16) Rockville, MD, USA
Center for Chemical Toxicology Research [email protected]
and Pharmacokinetics
College of Veterinary Medicine
North Carolina State University
Raleigh, NC, USA
Pharsight, Inc.
Cary, NC, USA
[email protected]
vii
viii Coauthors
Jim E. Riviere Xin - Rui Xia (3 )
Center for Chemical Toxicology Research Center for Chemical Toxicology Research
and Pharmacokinetics and Pharmacokinetics
Department of Population Health and Department of Population Health and
Pathobiology Pathobiology
College of Veterinary Medicine College of Veterinary Medicine
North Carolina State University North Carolina State University
Raleigh, NC, USA Raleigh, NC, USA
[email protected] [email protected]
Pierre - Louis Toutain (13)
UMR181 Physiopathologie et Toxicologie
Exp é rimentales INRA
Ecole Nationale V é t é rinaire de
Toulouse - 23
Chemin des Capelles – 31076
Toulouse, France
[email protected]
Preface
The second edition of C omparative Pharmacokinetics follows the fi rst edition ’ s goals of
providing the conceptual basis of pharmacokinetics as a tool for quantifying biological
processes encountered in comparative medicine.
The organization of this book remains the same whereby the basic principles of physiol-
ogy are introduced for systems involved in the absorption, distribution, metabolism, and
elimination (ADME) of chemicals and drugs in the body. This is followed by chapters
developing the primary approaches used in pharmacokinetic modeling today, namely com-
partmental, noncompartmental, population, and physiological approaches. Chapters on
nonlinear processes, dosage regimen construction, and statistical aspects of data analysis
are presented, followed by overviews of pharmacokinetic – pharmacodynamic (PK - PD)
modeling and specifi c applications on bioequivalence, disease effects, interspecies extra-
polations, and drug residues in food - producing animals.
As in the fi rst edition, this author has authored or coauthored all chapters for consistency.
New additions to this text include extensive revisions of the Distribution chapter coau-
thored by Jennifer Buur, the Hepatic Biotransformation chapter by Ronald Baynes, and the
Physiological Models chapter by Teresa Leavens. Chapters on Study Design and Population
Modeling by Jason Chittenden, Dosage Adjustment in Disease by Jennifer Davis, and
Tissue Residues by Sharon Mason have been expanded and revised. Pierre - Louis Toutain
comprehensively rewrote the PK - PD chapter as PK - PD modeling has become widespread
in comparative medicine. A new chapter on Quantitative Structure – Permeability
Relationships coauthored with Xin - Rui Xia has been added to illustrate how molecular
properties of chemicals and drugs are correlated to membrane transport, the basis of most
pharmacokinetic processes. Also, this chapter introduces basic statistical concepts of
regression analysis and study validation that are expounded upon later in the book. Finally,
the Bioequivalence chapter by Marilyn Martinez of the U.S. Food and Drug Administration
offers a complete regulatory perspective on determining product bioequivalence. This
chapter demonstrates many of the pharmacokinetic principles introduced in the earlier
chapters and adds in the requirements for statistical rigor needed for a regulatory approval.
All the remaining chapters have been revised and updated. In addition, cross - referencing
topics across all chapters has been expanded to help the reader to make important concep-
tual linkages between theory and applications.
This comparative and veterinary pharmacokinetics textbook serves as an introduction
to this discipline from the perspectives of physiology and medicine. The wide availability
ix
x Preface
of economic but powerful computers with comprehensive software packages can make
pharmacokinetic analysis seem automatic. A primary goal of this book is to ensure that
studies are properly designed before being conducted, that the proper models are used for
the end points in mind, and that resulting pharmacokinetic parameters are interpreted
correctly.
Jim E. Riviere
1 Introduction
Pharmacokinetics is best defi ned as the use of mathematical models to quantitate the time
course of drug absorption and disposition in man and animals. With the tremendous
advances in medicine and analytical chemistry, coupled with the almost universal avail-
ability of computers, what was once an arcane science has now entered the mainstream of
most fi elds of human and veterinary medicine. This discipline has allowed dosages of drugs
to be tailored to individuals or groups to optimize therapeutic effectiveness, minimize toxic-
ity, and avoid violative tissue residues in the case of food - producing animals.
What differentiates this discipline from other fi elds of pharmacology and medicine is
its focus on quantitating biological phenomena using various mathematical models and
restricting its purview to the movement of drugs and chemicals into, through, and out of
the body. The subsequent effects of these drugs on biological processes fall in the realm
of pharmacodynamics (PD), which is beyond the scope of the present pharmacokinetic text
but is extensively reviewed in Chapter 13 when linkage to pharmacokinetic models is
developed. There are numerous applications of pharmacokinetics in clinical practice, some
of them unknown to the practitioner as actually being pharmacokinetic modeling exercises
since the terminology has become embedded into the lexicon of general medicine.
Since the publication of the fi rst comparative pharmacokinetics text by Desmond Baggot
in 1 977, there has been explosive growth in all aspects of this discipline. This growth has
continued after the publication of the fi rst edition of the present text in 1999 and the release
in 2004 of the pivotal UK “ PK and PK - PD in Veterinary Medicine ” workshop (Lees, 2004 ).
The continued integration of pharmacokinetic concepts into global veterinary drug regula-
tions further fuels this growth, a development that can be appreciated by reading Chapter
15 on regulatory aspects of drug product bioequivalence.
The primary pharmacokinetic models originally utilized by comparative and veterinary
pharmacokineticists were the classic open compartmental models. These models, fi rst
clearly elucidated by Teorell in 1 937, have been the mainstay of pharmacokinetics for
much of the last decade. However, the use of noncompartmental models, especially those
based on statistical moment analyses, has recently expanded across multiple areas. This
popularity can be linked in part to a superb suitability for analysis by digital computers.
Paradoxically, many of the properties that make the analysis of serum pharmacokinetic
data amenable to exponential equations result from a few mathematical peculiarities in
the solution of these compartmental models. Newer noncompartmental approaches to
Comparative Pharmacokinetics: Principles, Techniques, and Applications, Second Edition. Jim E. Riviere.
© 2011 Jim E. Riviere. Published 2011 by John Wiley & Sons, Inc. ISBN: 978-0-813-82993-7
3