2nd Edition

Pharmacokinetics

Edited By Milo Gibaldi, Donald Perrier Copyright 1982

    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