1st Edition

Pharmacokinetic Principles of Dosing Adjustments Understanding the Basics

By Ronald D. Schoenwald Copyright 2000

    This book has evolved over the last twenty years from a cumulative effort to develop a professional course in pharmacokinetics that would assist future practitioners in therapeutic decision making. As practicing pharmacists become more involved with patient advising, it becomes apparent that clinicians will be required to make dosing adjustments for certain drugs. This will become increasingly more likely as pharmacy practitioners have access to patient information that requires careful attention to dose and dosing interval, which in turn correlates to various pharmacokinetic parameters such as half-life and the volume of distribution of drugs.

    Although many handbooks are available on this subject, they do not devote more than a brief chapter to the concepts behind the dosing adjustment approach. Pharmacokinetic Principles of Dosing Adjustments provides the concepts used to formulate approaches. Equations that appear in various chapters are developed, not through lengthy derivations, but by more of an intuitive approach. The equations are presented in their conceptual form, rather than a separate convenient form applicable to each clinic situation. This method is used to demonstrate how you can apply the initial conditions to the properties of the drug, patient and/or route of administration, rather than memorizing each variation of the basic equation. The author defines pertinent pharmacokinetic terms as well as kinetic processes and classical modeling relevant to dosing adjustments. Examples are included within each chapter that emphasize an understanding of the concepts.

    Pharmacokinetic Principles of Dosing Adjustments was written for practitioners who operate in a setting that requires careful consideration to dosing parameters and, in particular, with patients that require constant monitoring of therapeutic outcomes including dosing adjustments. Based on the introductory course in pharmacokinetics taught by Dr. Schoenwald for the past twenty years, this book is intended as a review and resource for practicing pharmacists.

    BASIC CONCEPTS

    Pharmacokinetic Processes
    Introduction
    Overview of Pharmacokinetic Processes
    Study Guide

    Kinetic Processes Applied to the Whole Body
    Introduction
    Classical Pharmacokinetic Models
    Justification for Application of a One-Compartment Model
    Study Guide

    Disposition Parameters of the One-Compartment Model
    Introduction
    Elimination Rate Constant
    Half-Life
    Volume of Distribution
    Area Under the Plasma Concentration-Time Curve
    Systemic Clearance
    Study Guide

    Parameters Used In Adjusting Doses
    Therapeutic Drug Monitoring and the Retrospective Approach
    Prospective Approach
    Urine Measurements of Drugs and Renal Clearance
    Dosage Adjustment in Renal Failure
    Hepatic Elimination and Dosing Adjustments
    Study Guide

    PARENTERAL DOSING ADJUSTMENTS

    Infusion
    Introduction
    Basic Infusion Principles
    Bolus Dose Plus Constant Rate Infusion
    Rapid Infusion Followed by Slow Infusion
    Intermittent Infusion
    Study Guide

    ORAL DOSING

    Important Parameters
    Introduction
    Fraction Absorbed (F)
    Absorption Rate Constant
    Factors Affecting the Absorption of Drugs
    Study Guide

    Bioavailability/Bioequivalence
    Introduction
    Definitions
    Bioavailability Measurements
    Bioequivalence
    Generic Substitution
    Study Guide

    Multiple Dosing Regimens
    Introduction
    Superposition Principle and Multiple Dosing
    Multiple Dosing Factor
    Multiple Dosing Equations
    Accumulation
    Missed Dose
    Study Guide

    ADVANCED CONSIDERATIONS

    Two-Compartment Model
    Introduction
    Volumes of Distribution
    IV Infusion: Two-Compartment Model
    Dosing Strategies
    Advanced Considerations
    Study Guide

    An Introduction to Nonlinear Pharmacokinetics
    Introduction
    Application to Phenytoin Dosing Regimens
    Single-Point Method
    Bayesian Approach
    Study Guide

    Appendix: Study Guide Solutions

    Index

    Biography

    Ronald D. Schoenwald

    "...introductory text... With its concise presentation and user-friendly examples, this text would best be utilized in introductory pharmocokinetics courses at the undergraduate level. It would also be a valuable addition to the reference collection of any medical library or drug information center."
    -American Journal of Pharmaceutical Education, vol. 65, Fall 2001