Computational Pharmacokinetics: 1st Edition (Hardback) book cover

Computational Pharmacokinetics

1st Edition

By Anders Kallen

Chapman and Hall/CRC

184 pages | 43 B/W Illus.

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Hardback: 9781420060652
pub: 2007-07-19
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Description

Being that pharmacokinetics (PK) is the study of how the body handles various substances, it is not surprising that PK plays an important role in the early development of new drugs. However, the clinical research community widely believes that mathematics in some way blurs the true meaning of PK. Demonstrating that quite the opposite is true, Computational Pharmacokinetics outlines the fundamental concepts and models of PK from a mathematical perspective based on clinically relevant parameters.

After an introductory chapter, the book presents a noncompartmental approach to PK and discusses the numerical analysis of PK data, including a description of an absorption process through numerical deconvolution. The author then builds a simple physiological model to better understand PK volumes and compares this model to other methods. The book also introduces compartmental models, discusses their limitations, and creates a general-purpose type of model. The final chapter looks at the relationship between drug concentration and effect, known as PK/pharmacodynamics (PD) modeling.

With both a solid discussion of theory and the use of practical examples, this book will enable readers to thoroughly grasp the computational factors of PK modeling.

Reviews

"I was not disappointed . . . I highly recommend this book to anyone who wants to learn about mathematical models for characterizing pharmacokinetics and pharmacodynamics."

– Gary L. Rosner, University of Texas M.D. Anderson Cancer Center, in JASA, March 2009

"Overall, the book provides a good introduction to some of the problems in the area of PK modelling to which statistical methods are now being routinely applied."

– David Woods, University of Southampton, in Journal of the Royal Statistical Society

Table of Contents

INTRODUCTION

Goal with this book

A short course in pharmacokinetics

Overview of book disposition

Integrals and convolution

Linear kinetics and compartments

Markov processes and compartmental models

EMPIRICAL PHARMACOKINETICS

Problem specification and some notations

Distribution and elimination

Absorption

Multiple dosing

One compartment drugs with capacity limited elimination

A recirculation model

NUMERICAL METHODS FOR PK PARAMETER ESTIMATION

Introduction

Estimating the terminal elimination rate

Integral estimation

Numerical deconvolution

Population average vs. subject-specific approach

A real example

Pharmacokinetics in drug development

PHYSIOLOGICAL ASPECTS ON PHARMACOKINETICS

Some physiological preliminaries

Distribution volume

Events within an organ

Building a physiological PK model

Absorption from the intestines

An alternative liver model

MODELING THE DISTRIBUTION PROCESS

The peripheral space

Two-compartment models

Three-compartment models

A general model for distribution and elimination

Example: Distribution analysis of budesonide and fluticasone

The distribution model and the recirculation model

PK/PD MODELING

Therapeutic response

Modeling a simple agonist

Modeling an antagonist

Hysteresis and approaches to PD/PK modeling

Four types of turn-over models

Modeling considerations

REFERENCES

APPENDIX A: LINEAR ORDINARY DIFFERENTIAL EQUATIONS

Linear differential equations

Explicit formulas for 2-by-2 systems

APPENDIX B: KEY NOTATIONS

INDEX

About the Series

Chapman & Hall/CRC Biostatistics Series

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MAT029000
MATHEMATICS / Probability & Statistics / General
MED071000
MEDICAL / Pharmacology