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Amiloride‐induced changes in digoxin dynamics and kinetics: Abolition of digoxin‐induced inotropism with amiloride
Author(s) -
Waldorff S,
Hansen P B,
Kjærgård H,
Buch J,
Egeblad H,
Steiness E
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.144
Subject(s) - amiloride , digoxin , medicine , contractility , endocrinology , chemistry , sodium , heart failure , organic chemistry
Digoxin dynamics and kinetics were studied in six healthy subjects with and without amiloride. Amiloride increased mean renal digoxin clearance from 1.3 to 2.4 ml · kg −1 · min −1 (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 potassium concentration in the tubular cells provoked by amiloride. In contrast, the extrarenal clearance of digoxin was almost blocked by amiloride; it fell from a mean of 2.1 to 0.2 ml · kg −1 · min −1 (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 s = 0.750, p < 0.001). Pretreatment with amiloride abolished this relationship (r s = 0.307, p = NS). Blood pressure and echocardiographically determined left ventricular end‐diastolic diameter measurements indicated no changes in the left ventricular post‐ and preload. It is concluded that amiloride suppressed digoxin‐induced inotropism. Clinical Pharmacology and Therapeutics (1981) 30, 172–176; doi: 10.1038/clpt.1981.144