Bidirectional (positive/negative) interference of spironolactone, canrenone, and potassium canrenoate on serum digoxin measurement: elimination of interference by measuring free digoxin or using a chemiluminescent assay for digoxin.
Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with digoxin in clinical practice. Spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for digoxin, and can falsely elevate serum digoxin concentrations. Serum digoxin concentrations were falsely lowered when the microparticle enzyme immunoassay (MEIA) was used. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin activities were measured. We observed digoxin-like activities in the FPIA, but observed no activity with the MEIA or the chemiluminescent assay (CLIA). However, when serum digoxin pools prepared from patients receiving digoxin were supplemented with these compounds, we observed suppression of total digoxin levels with the MEIA. In contrast, no interference was observed in the presence of these compounds when CLIA was used for digoxin measurement. These compounds are strongly protein-bound, and no apparent digoxin activity was observed in the protein-free ultrafiltrate when drug-free sera were spiked with high levels of these compounds. Taking advantage of strong protein binding of these compounds and weak protein binding of digoxin (25%), interference of spironolactone, canrenone, and potassium canrenoate in FPIA and MEIA digoxin assays can be mostly eliminated by monitoring free digoxin concentration. Another approach to avoid this interference is to use the CLIA digoxin assay.
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA. Amitava.Dasgupta@uth.tmc.edu
Amitava
A
Dasgupta
Helene
H
Saffer
Alice
A
Wells
Pradip
P
Datta
D002191:Canrenoic Acid / Q000494:pharmacology; D002192:Canrenone / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000097:blood*; D004077:Digoxin / Q000097:blood*; D004347:Drug Interactions; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006801:Humans; D008163:Luminescent Measurements; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D015203:Reproducibility of Results; D013148:Spironolactone / Q000494:pharmacology
D002316:Cardiotonic Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D004077:Digoxin; D002192:Canrenone; D002191:Canrenoic Acid