Amiloride-induced changes in digoxin dynamics and kinetics: Abolition of digoxin-induced inotropism with amiloride

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Abstract
Digoxin dynamics and kinetics were studied in 6 healthy subjects with and without amiloride. Amiloride increased mean renal digoxin clearance from 1.3-2.4 ml/kg per min (P < 0.001) due to increased tubular secretion of digoxin, while the glomerular filtration rate was unchanged. This might be caused by an increase in intracellular K concentration in the tubular cells provoked by amiliride. The extrarenal clearance of digoxin was almost blocked by amiloride; it fell from a mean of 2.1 to 0.2 ml/kg per min (P < 0.025). Total body clearance tended to fall, but the decrease was not statistically significant. Evaluation of myocardial contractility by systolic time intervals revealed a concentration-response relationship between digoxin and changes in preejection period index when digoxin was given alone (r = 0.750, P < 0.001). Pretreatment with amiloride abolished this relationship (r = 0.307, P = NS). Blood pressure and ECG-determined left ventricular end-diastolic diameter measurements indicated no changes in the left ventricular post- and preload. Apparently, amiloride suppressed digoxin-induced inotropism.