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Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications

D J Sumner, A J Russell

    British Journal of Clinical Pharmacology
    |April 1, 1976
    PubMed
    Summary

    This study investigated digoxin kinetics in healthy volunteers. A three-compartment model revealed renal clearance similar to glomerular filtration rate, enabling optimized dosing strategies.

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    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Clinical Pharmacology

    Background:

    • Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
    • Understanding digoxin's pharmacokinetic profile is crucial for safe and effective therapeutic use.

    Purpose of the Study:

    • To investigate the kinetics of digoxin in healthy volunteers.
    • To develop a kinetic model for predicting digoxin tissue concentrations and guiding dosage regimens.

    Main Methods:

    • Utilized an isotopic tracer technique for precise measurement.
    • Employed a three-compartment open kinetic model.
    • Analyzed plasma, urinary, and faecal data.

    Main Results:

    • Established digoxin renal clearance at 119+/-10 ml/min, comparable to glomerular filtration rate (110+/-14 ml/min).

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  • Determined digoxin extra-renal clearance to be 47+/-7 ml/min.
  • Predicted that a single 1 mg oral loading dose achieves therapeutic concentrations within 4 hours.

    • Conclusions:

    • The proposed three-compartment model accurately describes digoxin kinetics.
    • Renal and extra-renal clearance values provide a basis for individualized digoxin dosing.
    • A simple formula can be derived for maintenance doses based on GFR, extra-renal clearance, and bioavailability.