The influence of calcium antagonists on plasma digoxin concentration

Several investigators have independently discovered that the calcium antagonist, verapamil, causes a 60-80% increase in plasma digoxin. Pharmacokinetic studies indicate, that the elevated plasma digoxin level is due to verapamil-induced inhibition of both renal and extrarenal digoxin clearance. No significant changes in single-dose digoxin pharmacokinetics were observed during nifedipine coadministration . To elucidate the clinical relevance of this interaction, we investigated the influence of verapamil on digoxin-induced inotropism as assessed from systolic time intervals. In single-dose trials, the verapamil-induced elevation of plasma digoxin was associated with a more sustained reduction in left ventricular ejection time as compared to control. Correspondingly, the concentration-response relationship of digoxin inotropism was unaffected by verapamil. In-vitro studies showed that verapamil had no influence on the number of digitalis receptors on human lymphocytes. In accordance, verapamil enhanced the digoxin-induced elevation of intracellular sodium concentration possibly reflecting an increased receptor effect. The plasma digoxin elevation resulting from verapamil coadministration seems cardioactive with regard to both inotropism and toxic effects.