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.
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