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Digoxin metabolism in patients

U Peters, L C Falk, S M Kalman

    Archives of Internal Medicine
    |July 1, 1978
    PubMed

    Insights

    Digoxin metabolism involves reducing the lactone ring, with an average of 12.4% of urinary cardenolides showing this reduction. This metabolic process was not affected by patient factors or other medications.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Cardiovascular Medicine

    Background:

    • Digoxin is a crucial medication for managing heart conditions like atrial fibrillation and heart failure.
    • Understanding digoxin's metabolic pathways is essential for optimizing patient treatment and minimizing adverse effects.
    • The reduction of digoxin's lactone ring is a known metabolic transformation, but its variability in patients requires further investigation.

    Purpose of the Study:

    • To investigate the extent of digoxin's lactone ring reduction in patients receiving the drug.
    • To identify potential factors influencing the metabolic reduction of digoxin.
    • To correlate urinary and blood levels of reduced digoxin metabolites.

    Main Methods:

    • Analysis of 24-hour urine samples from 100 patients undergoing digoxin therapy.
    • Quantification of lipid-extractable cardenolides with a reduced lactone ring.
    • Assessment of patient demographics, digoxin dosage, blood levels, and co-administered therapies.

    Main Results:

    • An average of 12.4% (±11%) of urinary cardenolides exhibited a reduced lactone ring, with a wide range (2.2%–52%).
    • Over half of the patients (53) excreted more than 10% reduced products, and seven excreted over 35%.
    • No significant influence of age, sex, digoxin dose, or blood levels on the reduction percentage was observed. Dihydrodigoxin was identified as a major metabolite in one patient with high excretion.

    Conclusions:

    • Significant inter-individual variability exists in the metabolic reduction of digoxin's lactone ring.
    • The extent of this metabolic transformation appears independent of common patient and drug-related factors.
    • Further research may be needed to elucidate the precise mechanisms and clinical implications of digoxin lactone ring reduction.

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