Effect of acute changes in serum digoxin concentration on renal digoxin clearance

The effect of acute alterations of serum digoxin concentration (S DIG ) on the renal clearance of digoxin (C DIG ) was studied in six normal subjects undergoing water diuresis. Digoxin in a 5% dextrose and water solution was infused at a rate of 0.01 µg/kg/min (low dose). One hour after the infusion began, three 20‐min urine samples for clearance determination were taken. The digoxin infusion rate was then increased to 0.05 µg/kg/min (high dose) and three additional urine samples were taken an hour later. With low doses of digoxin, the S DIG was (X̄ ± SD) 0.63 ± 0.08 ng/ml, C DIG was 252.3 ± 65.1 ml/min, inulin clearance (C IN ) was 96.8 ± 15.7 ml/min, the ratio C DIG /C IN was 2.59 ± 0.38, and renal blood flow (C PAH ) was 516 ± 90 ml/min. With the high‐dose infusion, S DIG rose to 3.23 ± 0.44 ng/ml; C IN , C DIG , C DIG /C IN , and C PAH remained stable. C DIG correlated strongly with both C IN and C PAH . We conclude that in normal subjects undergoing water diuresis, C DIG /C IN is not altered by acutely increasing S DIG , digoxin is extensively secreted by the nephron, and C DIG is linearly related to renal plasma flow. Clinical Pharmacology and Therapeutics (1984) 36, 478–484; doi: 10.1038/clpt.1984.207