| |
| |
| Preface | |
| |
| |
| |
| Introduction to Pharmacokinetics and Pharmacodynamics | |
| |
| |
| |
| Introduction: Drugs and Doses | |
| |
| |
| |
| Introduction to Pharmacodynamics | |
| |
| |
| |
| Introduction to Pharmacokinetics | |
| |
| |
| |
| Dose-Response Relationships | |
| |
| |
| |
| Therapeutic Range | |
| |
| |
| |
| Summary | |
| |
| |
| |
| Passage of Drugs Through Membranes | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Structure and Properties of Membranes | |
| |
| |
| |
| Passive Diffusion | |
| |
| |
| |
| Carrier-Mediated Processes: Transport Proteins | |
| |
| |
| |
| Drug Administration, Absorption, and Bioavailability | |
| |
| |
| |
| Introduction: Local and Systemic Drug Administration | |
| |
| |
| |
| Common Routes of Systemic Drug Administration | |
| |
| |
| |
| Overview of Oral Absorption | |
| |
| |
| |
| Extent of Drug Absorption | |
| |
| |
| |
| Determinants of the Bioavailability | |
| |
| |
| |
| Factors Controlling the Rate of Drug Absorption | |
| |
| |
| |
| Biopharmaceutics Classification System | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Drug Distribution | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Extent of Drug Distribution | |
| |
| |
| |
| Rate of Drug Distribution | |
| |
| |
| |
| Distribution of Drugs to the Central Nervous System | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Drug Elimination and Clearance | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Clearance | |
| |
| |
| |
| Renal Clearance | |
| |
| |
| |
| Hepatic Clearance | |
| |
| |
| |
| Measurement of Clearances | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Compartmental Models in Pharmacokinetics | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Expressions for Component Parts of the Dose-Plasma | |
| |
| |
| |
| Putting Everything Together: Compartments and Models | |
| |
| |
| |
| Examples of Complete Compartment Models | |
| |
| |
| |
| Use of Compartmental Models to Study Metabolite Pharmacokinetics | |
| |
| |
| |
| Selecting and Applying Models | |
| |
| |
| Problems | |
| |
| |
| Recommended Reading | |
| |
| |
| |
| Pharmacokinetics of an Intravenous Bolus Injection in a One-Compartment Model | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| One-Compartment Model | |
| |
| |
| |
| Pharmacokinetic Equations | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| |
| Application of the Model | |
| |
| |
| |
| Determination of Pharmacokinetic Parameters Experimentally | |
| |
| |
| |
| Pharmacokinetic Analysis in Clinical Practice | |
| |
| |
| Problems | |
| |
| |
| Recommended Reading | |
| |
| |
| |
| Pharmacokinetics of an Intravenous Bolus Injection in a Two-Compartment Model | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Tissue and Compartment Distribution of a Drug | |
| |
| |
| |
| Basic Equation | |
| |
| |
| |
| Relationship Between Macro and Micro Rate Constants | |
| |
| |
| |
| Primary Pharmacokinetic Parameters | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| |
| Determination of the Pharmacokinetic Parameters of the Two-Compartment Model | |
| |
| |
| |
| Clinical Application of the Two-Compartment Model | |
| |
| |
| Problems | |
| |
| |
| Recommended Reading | |
| |
| |
| |
| Pharmacokinetics of Extravascular Drug Administration | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Model for First-Order Absorption in a One-Compartment Model | |
| |
| |
| |
| Bioavailability | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| Problems | |
| |
| |
| Recommended Reading | |
| |
| |
| |
| Introduction to Noncompartmental Analysis | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Mean Residence Time | |
| |
| |
| |
| Determination of Other Important Pharmacokinetic Parameters | |
| |
| |
| |
| Different Routes of Administration | |
| |
| |
| |
| Application of Noncompartmental Analysis to Clinical Studies | |
| |
| |
| Problems | |
| |
| |
| |
| Pharmacokinetics of Intravenous Infusion in a One-Compartment Model | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Model and Equations | |
| |
| |
| |
| Steady-State Plasma Concentration | |
| |
| |
| |
| Loading Dose | |
| |
| |
| |
| Termination of Infusion | |
| |
| |
| |
| Individualization of Dosing Regimens | |
| |
| |
| Problems | |
| |
| |
| |
| Multiple Intravenous Bolus Injections in the One-Compartment Model | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Terms and Symbols Used in Multiple-Dosing Equations | |
| |
| |
| |
| Monoexponential Decay During a Dosing Interval | |
| |
| |
| |
| Basic Pharmacokinetic Equations for Multiple Doses | |
| |
| |
| |
| Steady State | |
| |
| |
| |
| Basic Formula Revisited | |
| |
| |
| |
| Pharmacokinetic-Guided Dosing Regimen Design | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Multiple Intermittent Infusions | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Steady-State Equations for Multiple Intermittent | |
| |
| |
| |
| Monoexponential Decay During a Dosing Interval: Dtermination of Peaks, Troughs, and Elimination Half-Life | |
| |
| |
| |
| Determination of the Volume of Distribution | |
| |
| |
| |
| Individualization of Dosing Regimens | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| Problems | |
| |
| |
| |
| Multiple Oral Doses | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Steady-State Equations | |
| |
| |
| |
| Equations Used Clinically to Individualize Oral Doses | |
| |
| |
| |
| Simulation Exercise | |
| |
| |
| Problems | |
| |
| |
| |
| Nonlinear Pharmacokinetics | |
| |
| |
| |
| Linear Pharmacokinetics | |
| |
| |
| |
| Nonlinear Processes in Absorption, Distribution, Metabolism, and Elimination | |
| |
| |
| |
| Pharmacokinetics of Capacity-Limited Metabolism | |
| |
| |
| |
| Phenytoin | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Introduction to Pharmacodynamic Models and Integrated Pharmacokinetic-Pharmacodynamic Models | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Classic Pharmacodynamic Models Based on Traditional Receptor Theory | |
| |
| |
| |
| Empirical Pharmacodynamic Models Used Clinically | |
| |
| |
| |
| Integrated PK-PD Models: E<sub>max</sub> Models Combined with a PK Model for Intravenous Bolus Infection in a One-Compartment Model | |
| |
| |
| |
| Hystersis and the Effect Compartment | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Mechanism-Based Integrated Pharmacokinetic-Pharmacodynamic Models | |
| |
| |
| |
| Introduction | |
| |
| |
| |
| Alternative Models for Drug-Receptor Interaction: Operational Model of Agonism | |
| |
| |
| |
| Physiological Turnover Model and Its Characteristics | |
| |
| |
| |
| Indirect Effect Models | |
| |
| |
| |
| Transduction and Transit Compartment Models | |
| |
| |
| |
| Tolerance Models | |
| |
| |
| |
| Irreversible Drug Effects | |
| |
| |
| |
| Disease Progression Models | |
| |
| |
| Problems | |
| |
| |
| References | |
| |
| |
| |
| Review of Exponents and Logarithms | |
| |
| |
| |
| Rates of Processes | |
| |
| |
| |
| Creation of Excel Worksheets for Pharmacokinetic Analysis | |
| |
| |
| |
| Derivation of Equations for Multiple Intravenous Bolus Injections | |
| |
| |
| |
| Summary of the Properties of the Fictitious Drugs Used in the Text | |
| |
| |
| |
| Computer Simulation Models. Glossary of Abbreviations and Symbols | |
| |
| |
| Index. | |