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 microgram/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 microgram/kg/min (high dose) and three additional urine samples were taken an hour later. With low doses of digoxin, the S DIG was (means +/- 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.