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A two-compartment model for digoxin disposition in dogs

S M Kalman, H G Güllner, T A Gibson

    Arzneimittel-Forschung
    |January 1, 1980
    PubMed
    Summary

    Digoxin elimination from heart and skeletal muscle was studied in dogs. Digoxin disappearance followed a two-compartment model in both plasma and tissues.

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    Area of Science:

    • Pharmacokinetics
    • Cardiovascular Pharmacology
    • Drug Metabolism

    Background:

    • Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
    • Understanding digoxin's tissue distribution and elimination is crucial for optimizing therapeutic use and managing toxicity.
    • Previous studies have focused on plasma levels, with less data on tissue-specific disappearance rates.

    Purpose of the Study:

    • To investigate the disappearance kinetics of digoxin from cardiac and skeletal muscle in a canine model.
    • To develop a mathematical model describing digoxin disposition and elimination in various tissues.
    • To correlate tissue digoxin levels with serum concentrations over time.

    Main Methods:

    • Sequential muscle biopsies (left ventricle, left atrial appendage, skeletal muscle) were performed on dogs over 48 hours post-digoxin administration.

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  • Radioactive 3H-digoxin was used to trace drug levels in tissue and serum.
  • A two-compartment open model was employed, utilizing a computer program to analyze disposition and elimination data.

    • Main Results:

    • Digoxin disappearance from plasma and all studied tissues (heart and skeletal muscle) was consistent with a two-compartment open model.
    • Quantitative data on digoxin elimination rates from specific cardiac and skeletal muscle compartments were obtained.
    • Serum digoxin levels were measured concurrently to establish correlations with tissue concentrations.

    Conclusions:

    • The two-compartment open model accurately describes digoxin elimination from cardiac and skeletal muscle tissue in dogs.
    • This study provides valuable insights into the tissue-specific pharmacokinetics of digoxin, aiding in dose-response and toxicity assessments.
    • The findings support the importance of considering tissue-level drug disposition in understanding digoxin's overall pharmacokinetic profile.