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Digoxigenin biotransformation

H Gault, J Kalra, L Longerich

    Clinical Pharmacology and Therapeutics
    |June 1, 1982
    PubMed
    Summary
    This summary is machine-generated.

    Digoxigenin biotransformation produces polar metabolites, primarily glucuronides of 3-epidigoxigenin, which can interfere with digoxin radioimmunoassays. These metabolites may significantly contribute to measured serum digoxin levels in patients.

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    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Analytical Chemistry
    • Biochemistry

    Background:

    • Digoxin is a widely used cardiac glycoside for treating heart failure.
    • Understanding digoxin's metabolic pathways is crucial for accurate therapeutic drug monitoring.
    • Radioimmunoassays are commonly used to measure serum digoxin concentrations.

    Purpose of the Study:

    • To investigate the biotransformation of digoxigenin in healthy subjects.
    • To identify and characterize the metabolites of digoxigenin in serum and urine.
    • To assess the potential contribution of digoxigenin metabolites to measured digoxin levels.

    Main Methods:

    • Administration of radiolabeled (3H-digoxigenin-12 alpha) and unlabeled digoxigenin to healthy subjects.
    • Analysis of serum and urine samples using high-pressure liquid chromatography (HPLC).

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  • Identification of metabolites based on chromatographic behavior and comparison with known standards.

    • Main Results:

    • Less than 26% of serum tritium activity at 30 minutes was digoxigenin; the remainder consisted of polar metabolites.
    • The primary identified polar metabolites were glucuronides of 3-epidigoxigenin.
    • A biotransformation pathway involving 3 beta-digoxigenin, 3-keto-digoxigenin, and 3-epidigoxigenin was proposed.
    • Extensive cross-reactivity was observed between digoxigenin metabolites and digoxin antisera.

    Conclusions:

    • Digoxigenin undergoes significant biotransformation to polar metabolites, including glucuronides of 3-epidigoxigenin.
    • These metabolites can contribute substantially to the serum digoxin concentration measured by radioimmunoassay.
    • The digoxigenin metabolic pathway may be clinically relevant in patients receiving digoxin therapy.