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Related Experiment Videos

Altered tissue digoxin uptake after a toxic dose.

K Taubert, W Shapiro

    Recent Advances in Studies on Cardiac Structure and Metabolism
    |January 1, 1975
    PubMed
    Summary
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    This study shows that digoxin concentrations in dog tissues vary significantly with dose. High doses led to higher serum levels and altered tissue distribution, suggesting kidney and tissue binding saturation, impacting cardiac effects.

    Area of Science:

    • Pharmacology
    • Cardiovascular Physiology
    • Toxicology

    Background:

    • Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
    • Understanding digoxin's tissue distribution and its relationship to cardiac effects is crucial for therapeutic management.
    • Previous studies have investigated digoxin distribution, but dose-dependent effects and tissue binding saturation require further elucidation.

    Purpose of the Study:

    • To investigate the tissue distribution of digoxin in dogs following intravenous administration of low and high doses.
    • To correlate digoxin tissue concentrations with cardiac effects, including left ventricular (LV) function and toxicity.
    • To examine the relationship between serum and tissue digoxin levels and the implications of altered binding.

    Main Methods:

    Related Experiment Videos

    • Intravenous administration of low (0.03 mg/kg) and high (0.14 mg/kg) doses of digoxin to dogs.
    • Serial serum sampling to monitor digoxin excretion and determine elimination phases.
    • Radioimmunoassay (RIA) for quantifying digoxin concentrations in serum and various tissue extracts (kidney, liver, pancreas, diaphragm, LV, RV, atria) post-mortem.

    Main Results:

    • Low dose (Group A) increased LV dP/dt, while high dose (Group B) induced arrhythmias or death.
    • Higher digoxin concentrations were observed in Group B across all tissues and serum (p < 0.001).
    • Toxic to therapeutic concentration ratios varied significantly across tissues, with serum-to-LV ratio lower in Group B (1:13) compared to Group A (1:32).

    Conclusions:

    • Myocardial toxicity correlated with increased tissue digoxin, but disproportionately high serum levels suggest kidney and tissue binding saturation.
    • Altered serum to tissue concentration ratios indicate that serum digoxin levels may not always linearly predict tissue content or cardiac effects.
    • These findings highlight the complex pharmacokinetics of digoxin and the importance of considering tissue binding dynamics in interpreting serum concentrations.