Abbott ARCHITECT clinical chemistry and immunoassay systems: digoxin assays are free of interferences from spironolactone, potassium canrenoate, and their common metabolite canrenone.

Spironolactone, which is metabolized to canrenone, is often used in combination with digoxin. Potassium canrenoate is a similar drug that is also metabolized to canrenone. As a result of reported interference of spironolactone, potassium canrenoate, and their common metabolite canrenone with digoxin immunoassays, we investigated potential interference of these compounds with two relatively new digoxin assays for application on ARCHITECT clinical chemistry platforms (cDig, particle-enhanced turbidimetric inhibition immunoassay) and ARCHITECT immunoassay platforms (iDig, chemiluminescent microparticle immunoassay), both from Abbott Diagnostics. When aliquots of drug-free serum pool were supplemented with various amounts of spironolactone, potassium canrenoate, and canrenone, no apparent digoxin concentration was observed using cDig assay on ARCHITECT c4000, c8000, and c16000 or iDig assay on i1000SR and i2000SR analyzers. In addition, we observed no false increase in serum digoxin value when aliquots of a digoxin pool were further supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone. We conclude that both the cDig and iDig assays on the ARCHITECT analyzers are free from interferences by spironolactone, potassium canrenoate, and canrenone.

Effect of spironolactone, potassium canrenoate and their common metabolite canrenone on serum digoxin measurement by digoxin III, a new digoxin immunoassay.

Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with several digoxin immunoassays at concentrations expected after therapeutic usage of these drugs and falsely elevate or lower serum digoxin concentrations. Recently, Abbott Laboratories marketed a new Digoxin III immunoassay for application on the AxSYM analyzer. We studied the potential interference of these compounds with this new digoxin assay. The Tina-quant assay was used as the reference method because spironolactone, potassium canrenoate, and canrenone do not interfere with serum digoxin measurement using this assay. Aliquots of drug-free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin concentrations were measured using the Digoxin III assay and Tina-quant assay. Significant apparent digoxin concentrations were observed when the Digoxin III digoxin assay was used, but no apparent digoxin levels was observed using the Tina-quant assay. When serum pools prepared from patients receiving digoxin were further supplemented with these compounds in concentrations expected in sera of patients receiving these medications, falsely elevated digoxin levels were observed using Digoxin III assay, but no statistically significant change was observed using the Tina-quant assay. We conclude that spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with the serum digoxin measurements using the new Digoxin III assay.

Adaptation to chronic potassium loading in normal man.

To analyze factors involved in the maintenance of potassium balance during increased intake, 6 healthy males were studied on a normal (80 mEq) and high (300 mEq) potassium diet. After 18 days of potassium-rich diet, urinary potassium excretion had increased from 50 +/- 12 to 233 +/- 45 mEq/day. Plasma renin activity and body weight were unchanged, serum potassium and plasma aldosterone somewhat increased, and the ratio of plasma aldosterone to renin activity consistently elevated. Acetazolamide injection (1 g i.v.) increased sodium and potassium excretion rates equally on the two diets indicating that a sudden increase in distal solute delivery was not handled differently after potassium loading. The reaction to a high dose of aldosterone (1 mg i.v. followed by 0.5 mg/h infusion) in terms of sodium retention and potassium excretion was also comparable, indicating no altered sensitivity to aldosterone after adaptation to the potassium-rich diet. By contrast, the aldosterone antagonist canrenoate (100 mg i.v.) acutely raised NaCl excretion without changing the potassium excretion during the high potassium diet, but did not affect NaCl excretion during the normal diet. Subsequent oral administration of spironolactone for 5 days (200 mg daily) caused a more negative sodium balance associated with more weight loss and rise in renin activity during the potassium rich diet. Surprisingly we noticed no fall in renal potassium excretion in this period, but mean serum potassium was raised by 0.3-0.4 mEq/l at the end. These results suggest that adaptation of a healthy subject to a potassium-rich diet does not involve intrinsic changes of the distal tubule, but a shift of sodium reabsorption from a proximal to a distal (aldosterone-sensitive) nephron level.(ABSTRACT TRUNCATED AT 250 WORDS)