Clinical Chemistry
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Clinical Chemistry 25: 48-50, 1979;
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Clinical Chemistry, Vol 25, 48-50, Copyright © 1979 by American Association for Clinical Chemistry

Spironolactone-associated digoxin radioimmunoassay interference

B Silber, LB Sheiner, JL Powers, ME Winter and W Sadee

Apparent digoxin was measured in the serum of 21 patients receiving spironolactone and in 21 controls, by use of a sequential-saturation 3H- radioimmunoassay (RIA) and an equilibrium 125I-RIA. No patient had been given digoxin for at least four weeks. "Digoxin" values in the former group were significantly (p less than 0.05) higher than in the control group, and often were in or near the "therapeutic" range by the equilibrium 125I-RIA, but not by the sequential-saturation 3H-RIA. Canrenone (a major active metabolite of spironolactone) in the serum of the former group was measured by a newly developed liquid- chromatographic technique and correlated (r = 0.73) with "digoxin" concentrations by the 125I-RIA. However, external addition of canrenone to control serum in comparable concentrations did not cause appreciable "digoxin" values by the 125I-RIA. These findings suggest that other metabolites of spironolactone are responsible for the assay interference, the degree of which appears to depend on antibody specificity. Therefore, assay specificity should be established in clinical laboratories by using digoxin-free serum from patients ingesting spironolactone, and not by using spironolactone- or canrenone- fortified digoxin-free serum.


The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
W. Steimer, C. Muller, and B. Eber
Digoxin Assays: Frequent, Substantial, and Potentially Dangerous Interference by Spironolactone, Canrenone, and Other Steroids
Clin. Chem., March 1, 2002; 48(3): 507 - 516.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
J. A. Paladino, K. H. Davidson, and B. B. McCall
Influence of Spironolactone on Serum Digoxin Concentration
JAMA, January 27, 1984; 251(4): 470 - 471.
[Abstract] [PDF]

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 ANN INTERN MEDHome page
S. W. GRAVES, B. BROWN, and R. VALDES Jr.
An Endogenous Digoxin-Like Substance in Patients with Renal Impairment
Ann Intern Med, November 1, 1983; 99(5): 604 - 608.
[Abstract] [PDF]


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Copyright © 1979 by the American Association for Clinical Chemistry.