Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations. Sheila Annie Peters

      

      Table of Contents

      1  COVER

      2  TITLE PAGE

      3  COPYRIGHT PAGE

      4  DEDICATION PAGE

      5  PREFACE TO THE SECOND EDITION

      6  PREFACE TO THE FIRST EDITION

      7  ACKNOWLEDGMENTS

      8  ABOUT THE COMPANION WEBSITE

      9  SECTION I: PRINCIPLES, METHODS AND BACKGROUND INFORMATION 1 A REVIEW OF PHARMACOKINETIC AND PHARMACODYNAMIC PRINCIPLES 1.1 INTRODUCTION 1.2 PHARMACOKINETIC PRINCIPLES 1.3 PHARMACOKINETIC VARIABILITY 1.4 PHARMACOKINETICS OPTIMIZATION IN DRUG DISCOVERY 1.5 PHARMACODYNAMIC PRINCIPLES KEYWORDS REFERENCES 2 A REVIEW OF DRUG–DRUG INTERACTIONS 2.1 INTRODUCTION 2.2 DRUG INTERACTIONS MEDIATED BY ENZYMES AND TRANSPORTERS AT VARIOUS SITES 2.3 FACTORS AFFECTING DDI 2.4 IN VITRO METHODS TO EVALUATE DRUG–DRUG INTERACTIONS 2.5 SOURCES OF UNCERTAINTY 2.6 THERAPEUTIC PROTEIN–DRUG INTERACTION KEYWORDS REFERENCES 3 MODELING PHARMACOKINETICS, PHARMACODYNAMICS, AND DRUG INTERACTIONS 3.1 INTRODUCTION 3.2 MODELING PHARMACOKINETICS 3.3 PHARMACOKINETICS/PHARMACODYNAMICS AND PK/EFFICACY (EXPOSURE/RESPONSE) MODELING 3.4 PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING AND ITS INTEGRATION WITH PHARMACODYNAMICS AND EFFICACY MODELS KEYWORDS REFERENCES 4 PHYSIOLOGICAL MODEL FOR ABSORPTION 4.1 INTRODUCTION 4.2 DRUG ABSORPTION AND GUT BIOAVAILABILITY 4.3 FACTORS AFFECTING DRUG ABSORPTION AND GUT BIOAVAILABILITY 4.4 IN SILICO PREDICTIONS OF PASSIVE PERMEABILITY AND SOLUBILITY 4.5 MEASUREMENT OF PERMEABILITY, SOLUBILITY, LUMINAL STABILITY, EFFLUX, INTESTINAL METABOLISM 4.6 ABSORPTION MODELING KEYWORDS REFERENCES 5 PHYSIOLOGICAL MODEL FOR DISTRIBUTION 5.1 INTRODUCTION 5.2 FACTORS AFFECTING TISSUE DISTRIBUTION OF XENOBIOTICS 5.3 IN SILICO MODELS OF TISSUE PARTITION COEFFICIENTS 5.4 MEASUREMENT OF PARAMETERS REPRESENTING THE RATE AND EXTENT OF TISSUE DISTRIBUTION 5.5 PHYSIOLOGICAL MODEL FOR DRUG DISTRIBUTION 5.6 DRUG CONCENTRATIONS AT THE SITE OF ACTION KEYWORDS REFERENCES 6 PHYSIOLOGICAL MODELS FOR DRUG METABOLISM AND EXCRETION 6.1 INTRODUCTION 6.2 FACTORS AFFECTING DRUG METABOLISM AND EXCRETION OF XENOBIOTICS 6.3 MODELS FOR HEPATOBILIARY AND RENAL EXCRETION 6.4 PHYSIOLOGICAL MODELS REFERENCES 7 GENERIC WHOLE‐BODY PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING 7.1 INTRODUCTION 7.2 STRUCTURE OF A GENERIC PHYSIOLOGICALLY‐BASED PHARMACOKINETIC (PBPK) MODEL 7.3 SOMATIC COMPARTMENTS 7.4 MODEL ASSUMPTIONS 7.5 PBPK SOFTWARE REFERENCES 8 PBPK MODELING OF BIOTHERAPEUTICS 8.1 INTRODUCTION 8.2 THERAPEUTIC PROTEINS 8.3 PHARMACOKINETICS OF THERAPEUTIC PROTEINS 8.4 PBPK MODELING OF MONOCLONAL ANTIBODIES