This book is based on research papers and commentaries on pharmacokinetic methods and applications published since 1975. It offers detailed examinations of new developments in the pharmacokinetic field with enhanced clarity of presentation and simplified organization.
Preface
One-Compartment Model
Intravenous Injection
Intravenous Infusion
First-Order Absorption
Apparent Zero-Order Absorption
References
Multicompartment Models
Intravenous Injection
Intravenous Infusion
First-Order Absorption
Determination of Pharmacokinetic Parameters
References
Multiple Dosing
Intravenous Administration
Intravenous Infusion
First-Order Absorption
Determination of Pharmacokinetic Parameters from Multiple-Dosing Data
References
Absorption Kinetics and Bioavailability
Absorption Rate
Extent of Absorption
Statistical Considerations in Comparative Bioavailability Studies
Sustained Release
References
Apparent Volume of Distribution
Relationship Between Volume of Distribution, Drug Binding and Elimination, and Anatomic Volume
Tissue Binding
Estimation of Apparent Volumes of Distribution
References
Kinetics of Pharmacologic Response
Kinetics of Directly Reversible Pharmacologic Response
Kinetics of Indirect Pharmacologic Response
Kinetics of Irreversible Pharmacologic Response
Appendix: Solutions for Cs, Cr, and CT for Cell Systems Sensitive to Drugs That are Cell Cycle Specific
References
Nonlinear Pharmacokinetics
Michaelis-Menten Kinetics
Some Pharmacokinetic Characteristics of Michaelis-Menten Processes
In Vivo Estimation of Km and V m
Clearance, Half-Life, and Volume of Distribution
Drug Concentration at Steady State
Time to Steady State
Area Under the Curve and Bioavailability
Composition of Urinary Excretion Products
Other Nonlinear Elimination Processes
Enzyme Induction
Nonlinear Binding
Some Problems in Quantifying Nonlinear Pharmacokinetics
References
Clearance Concepts
Organ Clearance
Total Clearance
Hepatic Clearance
Hepatic Clearance and Drug Binding in Blood
Drug Binding and Free Drug Concentration
Half- Life, Intrinsic Clearance, and Binding
First-Pass Effect
Gut Wall Clearance
Lung Clearance
Renal Clearance
Clearance Concepts Applied to Metabolites
Physical Models of Organ Clearance
Blood Clearance Versus Plasma Clearance
References
Physiological Pharmacokinetlc Models
Blood Flow Rate-Limited Models
Experimental Considerations
Blood Clearance
Lung Clearance
Apparent Volume of Distribution
Nonlinear Disposition
Membrane-Limited Models
Species Similarity and Scale-Up
References
Application of Pharmacokinetic Principles
Multiple Dosing
Dose Adjustments in Renal Failure
Hemodialysis
Methods for Determination of Individual Patient Parameters
References
Noncompartmental Analysis Based on Statistical Moment
Theory
Statistical Moments
Bioavailability
Clearance
Half-Life
Absorption Kinetics
Apparent Volume of Distribution
Fraction Metabolized
Predicting Steady-State Concentrations
Predicting Time to Steady State
Conclusions
References
Appendix A Method of Laplace Transforms
References
Appendix B Method for Solving Linear Mammillary Models
References
Appendix C Method of Residuals
Appendix D Estimation of Areas
Reference
Appendix E Prediction of Drug Concentrations on Multiple Dosing Using the Principle of Superposition
References
Appendix F Estimation of Rates
Reference
Appendix G Selective Derivations
Michaelis-Menten Equation
Time To Reach a Fraction of Steady State for a Drug Eliminated by Parallel First-Order and Capacity-Limited Processes
Reference
Appendix H Computer Programs
References
Author Index
Subject Index
Biography
Milo Gibaldi, Donald Perrier
