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.
D004077:Digoxin / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects; D012964:Sodium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D011955:Receptors, Drug; C028996:cardiac glycoside receptors; D004077:Digoxin; D012964:Sodium; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase