The renal clearance of digoxin is dependent upon the serum digoxin concentration.

The effect of alterations of serum digoxin concentrations on the renal clearance of digoxin (CDIG) was studied in seven dogs. Digoxin, 0.016 microgram/kg/min (low dose) in normal saline was infused at the rate of 1 ml/min. After 60 min of equilibration, five 15-min urine collections were made. The digoxin infusion was then increased to 0.112 microgram/kg/min (high dose) and five additional collections were made after equilibration. Digoxin was measured by 125I radioimmunoassay whose specificity was confirmed by high-pressure liquid chromatography. With low dose digoxin, the serum digoxin concentration was 0.5 +/- 0.2 (S.D.) ng/ml, CDIG 58 +/- 26 ml/min, inulin clearance (CIN) 48 +/- 8 ml/min and CDIG/CIN 1.2 +/- 0.5. With high dose infusion, the serum digoxin concentration rose to 5.2 +/- 1.4 ng/ml, CDIG decreased 43% to 33 +/- 13 ml/min and CDIG/CIN decreased 48% to 0.6 +/- 0.2 (P < .05 for both compared to control, while CIN remained constant. We conclude that CDIG is not as dependent upon glomerular filtration as previously thought. Increases in serum digoxin concentrations can significantly reduce CDIG without altering glomerular filtration rate.