Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration

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Abstract
Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, single-dose digoxin kinetics were evaluated along with repeated measurements of intraerythrocytic Na concentration in 8 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 per kg and prolonged digoxin biologic t1/2 [half-life] from 33.5 .+-. 2.4 to 41.4 .+-. 2.3 h. These kinetic changes were associated with a greater elevation of intraerythrocytic Na concentration than controls. Verapamil had no effect on intraerythrocytic Na content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular Na concentration correlates closely with clinical signs of digoxin toxicity, verapamil may increase the risk of digoxin-induced arrhythmias.