IVD
For in vitro diagnostic use.
Elecsys® Digoxin
Digoxin is a widely prescribed steroidal cardio-active glycoside. It acts by binding and inhibiting the Na+ /K+ -ATPase which in the end increases the intracellular Ca2+ concentration.1,2 This results in a positive inotrope effect which makes digoxin a beneficial drug for heart failure. It improves the strength of myocardial contraction and results in the beneficial effects of increased cardiac output, increased Left Ventricular Ejection Fraction, and decreased Pulmonary Capillary Wedge pressure.3,4 Digoxin therapy also results in stabilized and slowed ventricular pulse rate.5Although the availability of crystalline digoxin has permitted the standardization of drug dosage, therapeutic administration inadvertently, yet frequently, results in toxicity. Importantly, symptoms of digoxin toxicity often mimic the cardiac arrhythmias for which the drug was originally prescribed. Digoxin concentrations of 0.9‑2.0 ng/mL in serum or plasma were considered to be therapeutic.6,7 However, later studies observed an increased risk for mortality for digoxin concentrations of 1.2 ng/mL and higher.8,9 The 2013 AHA/ACC guidelines mentioned that doses of digoxin that achieve a plasma concentration of drug in the range of 0.5 to 0.9 ng/mL aresuggested, given the limited evidence currently available and that overt digoxin toxicity is commonly associated with serum digoxin levels >2 ng/mL.10Toxicity of digoxin may reflect several factors:The drug has a low therapeutic ratio (i.e. a very small difference exists between therapeutic and toxic tissue levels);Individuals vary in their response to digoxin;Absorption of various tablet forms of digoxin may vary over a two-fold range;11,12Susceptibility to digitalis toxicity apparently increases with age mainly associated with renal impairment.4,13In combination with other clinical data, monitoring serum or plasma levels may provide the physician with useful information to aid in adjusting patient dosage, and achieving optimal therapeutic effect, while avoiding both subtherapeutic and harmful toxic drug levels.14The Elecsys Digoxin assay employs a competitive test principle using a monoclonal antibody specifically directed against digoxin. Digoxin in the sample competes with the added digoxin derivative labeled with biotin for the binding sites on the ruthenylated antibody-complex.a)a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy)32+)1 Hauptman PJ, Kelly RA. Digitalis. Circulation 1999;99:1265-1270.2 Katz A, Lifshitz Y, Bab-Dinitz E, et al. Selectivity of Digitalis Glycosides for Isoforms of Human Na,K-ATPase. J Biol Chem 2010 Jun;285(25) 19582-19592.3 Eichhorn EJ, Gheorghiade M. Digoxin. Progress Cardiovasc Diseases 2002 Jan/Feb;44(4):251-266.4 Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary Use of Digoxin in the Management of Cardiovascular Disorders. Circulation 2006;113:2556-2564.5 Hoffman BF, Bigger JT Jr. In: Gilman AG, Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. 6th ed. New York, NY: MacMillan; 1980:729-760.6 Oellerich M. Pharmaka (Drug monitoring). In: Thomas L (ed.). Labor und Diagnose, TH-Books, Frankfurt, 5. edition, 1998:1174. Englisch: Clinical Laboratory. 1st English Edition 1998:1151.7 Jortani SA, Valdes R Jr. Digoxin and Its Related Endogenous Factors. Critical Reviews Clin Lab Sci 1997;34(3):225-274.8 Rathore SS, Curtis JP, Wang Y, et al. Association of Serum Digoxin Concentration and Outcome in Patients with Heart Failure. JAMA 2003 Feb;289(7):871-878.9 Adams KF, Patterson JH, Gattis WA, et al. Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group Trail. J Am Coll Cardiology 2005;46(3):497-504.10 Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62(16):e147-e239.11 Lindenbaum J, Mellow MH, Blackstone MO, et al. Variation in Biologic Availability of Digoxin from Four Preparations. New Engl J Med 1971;285:1344-1347.12 LindenbaumJ, Butler VP Jr., Murphy JE, et al. Correlation of Digoxin- Tablet Dissolution Rate with Biological Availability. Lancet 1973;1:1215-1217.13 Jelinek HF, Warner P. Digoxin therapy in the elderly: pharmacokinetic considerations in nursing. Geriatr Nurs. 2011;4:263-269.14 Butler VP Jr., Lindenbaum J. Serum Digitalis Measurements in the Assessment of Digitalis Resistance and Sensitivity. Am J Med 1975;58:460-469.
