Renal tubular secretion of digoxin.

SUMMARY To study the mechanism of the renal handling of digoxin, simultaneous measurements of digoxin and inulin clearances were performed in 13 digitalized patients with congestive heart disease. The renal digoxin clearances exceeded inulin clearances, indicating an active tubular secretion of digoxin. No evidence of tubular backward diffusion was disclosed. Treatment with spironolactone (Aldactone) decreased the digoxin clearances, suggesting an inhibition of the tubular secretion of digoxin in the distal segment of the renal tubulus. After blocking the tubular secretion, the calculated renal clearances of nonproteinbound digoxin in plasma were similar to that of inulin, suggesting a glomerular filtration of free plasma digoxin. Plasma digox-in level rose during treatment with spironolactone. Spironolactone DIGOXIN IS predominantly eliminated through the kidneys; excretion is greatly impaired in patients with advanced renal failure.' It is primarily excreted both in normal individuals and in patients with congestive heart failure, as the unchanged glycoside.2 6 Several authors have demonstrated that the renal clearance of digoxin calculated from the total plasma digoxin concentration is equal to the endogenous creatinine clearance,7~1' which, in man, approximates the glomerular filtration rate (GFR). However, about 25% of plasma digoxin is bound to protein'2' 13 and not available for filtration, suggesting that digoxin is subject to tubular secretion. The present study was undertaken for a closer evaluation of the mechanism of the renal handling of digoxin in digitalized patients. Simultaneous deter-minations of digoxin and inulin clearance were performed since inulin is the accepted standard for measurement of the GFR. The observation of a significantly reduced digoxin clearance in a patient (not included in this series) who received spironolac-tone caused me to repeat the clearance deter-minations, when possible, after treatment with spironolactone. Cardiac glycosides Patients and Methods Patients Studies were performed on 13 hospitalized adult patients with chronic congestive heart disease. The pertinent clinical information is listed in table 1. None of the patients gave a history of renal disease. Five had slightly elevated serum creatinine levels, but none had proteinuria, and the urinary sediments were normal. All the patients had been on a stable oral maintenance digoxin dose (table 1) for more than one month prior to the study and presented no clinical or electrocardiographic evidence of digitalis toxicity. The bioavailability of the tablets was not studied; however, each patient received tablets from the same batch throughout the study. In addition to digoxin all the patients received only furosemide (40-160 mg daily) …