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Digoxin biotransformation.

M H Gault, L L Longerich, J C Loo

    Clinical Pharmacology and Therapeutics
    |January 1, 1984
    PubMed
    Summary
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    Digoxin biotransformation in patients with end-stage renal failure (ESRF) revealed significant polar metabolites. These metabolites, potentially impacting radioimmunoassay results, suggest extensive digoxin metabolism in ESRF patients.

    Area of Science:

    • Pharmacokinetics
    • Renal Physiology
    • Analytical Chemistry

    Background:

    • Digoxin is a crucial cardiac glycoside for heart failure management.
    • Renal impairment significantly affects drug clearance and metabolism.
    • Understanding digoxin metabolism in end-stage renal failure (ESRF) is vital for therapeutic drug monitoring.

    Purpose of the Study:

    • To investigate the serum and urine digoxin and metabolite profiles in dialysis-dependent ESRF patients versus those with normal renal function.
    • To identify and quantify digoxin metabolites.
    • To assess the impact of metabolites on standard digoxin radioimmunoassays.

    Main Methods:

    • High-performance liquid chromatography (HPLC) assay for serum and urine digoxin and metabolites.
    • Administration of radiolabeled 3H-digoxin (150 μCi).

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  • Study groups: 10 ESRF patients (Group I) and 5 patients with normal renal function (Group II).
  • Analysis of 13 patients on maintenance digoxin therapy at steady state.

    • Main Results:

    • Regularly detected metabolites included 3β-digoxigenin, its digitoxosides, 3-keto, and 3α(epi)-digoxigenin.
    • Polar metabolites were quantitatively abundant, averaging 26% of plasma radioactivity and 60% of digoxin at 6 hours.
    • No significant differences in polar metabolite or digoxin levels were observed between ESRF and normal renal function groups.
    • Metabolites showed varying reactivity with digoxin antibodies, potentially influencing radioimmunoassay results.

    Conclusions:

    • Digoxin undergoes extensive biotransformation in some patients, primarily through hydrolysis, oxidation, epimerization, and conjugation.
    • Polar metabolites represent a significant portion of circulating digoxin-related compounds.
    • The presence of digoxin metabolites may interfere with standard radioimmunoassay quantification of serum digoxin concentrations.