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Verapamil‐induced changes in digoxin kinetics and intraerythrocytic sodium concentration
Author(s) -
Pedersen Knud Erik,
Christiansen Bent Dorff,
Kjaer Karen,
Klitgaard Niels Anders,
NielsenKudsk Folmer
Publication year - 1983
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.1983.121
Subject(s) - verapamil , digoxin , pharmacology , cardiac glycoside , sodium , chemistry , intracellular , toxicity , medicine , ouabain , calcium , biochemistry , heart failure , organic chemistry
Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, we evaluated single‐dose digoxin kinetics along with repeated measurements of intraerythrocytic sodium concentration in eight healthy subjects before and during verapamil coadministration. Verapamil reduced mean total body clearance of digoxin from 4.68 ± 0.41 to 3.29 ± 0.26 ml/min/kg and prolonged digoxin biologic t½ from 33.5 ± 2.4 to 41.4 ± 2.3 hr. These kinetic changes were associated with a greater elevation of intraerythrocytic sodium concentration than controls. Verapamil had no effect on intraerythrocytic sodium content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular sodium concentration has proved to correlate closely with clinical signs of digoxin toxicity, our data indicate that verapamil is likely to increase the risk of digoxin‐induced arrhythmias. Clinical Pharmacology and Therapeutics (1983) 34, 8–13; doi: 10.1038/clpt.1983.121