Kallen Computational Pharmacokinetics

Erscheinungsjahr 2007
ISBN: 978-1-4200-6066-9
Verlag: Taylor & Francis
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 184 Seiten

Reihe: Chapman & Hall/CRC Biostatistics Series

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.

Zielgruppe

Statisticians in the pharmaceutical industry, pharmacokineticists, and applied mathematics students.

Autoren/Hrsg.

Kallen, Anders

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie

Inhaltsverzeichnis

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