digoxin in serum/plasma

Indications

• therapeutic drug monitoring, digoxin therapy
  • atrial fibrillation, atrial flutter
  • heart failure
  • paroxyxsmal atrial tachycardia

Reference interval

• Therapeutic Range*
  • 0.8 - 2.0 ng/mL
  • 0.5 - 1.0 ng/mL
  • 0.5 - 0.8 ng/mL
  • 0.5 - 0.9 ng/mL
• Toxic Range: > 2.0 ng/mL

*anything reading < 0.3 ng/mL is below the linearity of the instrument

* increased mortality with digoxin levels > 0.9 ng/mL (men)

Principle

The clinical use of cardiac glycosides is complicated by a high incidence of toxicity. The introduction by Smith, Butler & Haber of radioimmunoassay for measurement of serum levels of digoxin has made it possible to closely monitor digoxin patients. Doherty showed a rather constant relationship between serum & myocardial tissue levels of digoxin. Thus, the measurement of serum digoxin levels provides useful information in the management of digitalized patients. The assay is useful for the determination of levels of active drug, drug availability for various dosage forms, determination of possible overdoses & evaluation of response with high risk of toxicity.

The Stratus Fluorometric Enzyme Immunoassay System is a rapid & sensitive automated procedure for the determination of therapeutic drug levels in serum or plasma. The digoxin assay can be completed at the rate of approximately 60 samples per hour & is sensitive to nanogram levels of digoxin, i.e. from 0.3 ng/mL up to 4 ng/mL.

The Stratus Digoxin assay procedure is based upon a sequential saturation methodology. In the sequential methodology, a free drug is allowed initially to bind to digoxin antibody in the center portion of a square piece of glass fiber paper. The remaining unbound antibody sites are titrated by the addition of enzyme-labeled drug (conjugate). The unbound conjugate is later washed from the field of view of the fluorometer by applying a wash solution to the center of the reaction zone & removing the unbound fraction by radial elution. By including substrate for the enzyme within the wash. The enzymatic rate of the bound fraction can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessors within the analyzer.

To perform measurements, plastic carriers (tabs) containing the antibody immobilized on glass fiber paper are placed into the analyzer loading station. These tabs are subsequently transferred to a circular rotating track where they pass through a series of 'work' stations. At the initial station a transfer mechanism aspirates an aliquot of patient sample from the sample carousel and delivers it to the tab. Conjugate & substrate wash are added at subsequent stations. At the final step, the tab moves to the 'read' station where the quantity of bound conjugate is monitored via front surface fluorometry.

Clinical significance

Digoxin is a cardiac glycoside that restores the force of cardiac contraction in congestive heart failure. It is also used in management of supraventricular tachycardia.

At low concentration, digoxin causes the atrium to electrically excitable. Moderate concentrations of digoxin are required to reduce the rate of depolarization in the spontaneously depolarizing conductive fibers (Purkinje fibers), & high toxic concentrations of digoxin are necessary to diminish depolarization of the ventricular myocardium.

Disagreement over the clinical value of digoxin measurements & the failure of the digoxin concentration to correlate with clinical toxicity are usually related to aberrations in serum & tissue concentrations of sodium, potassium, magnesium, & calcium. An increase sensitivity to digoxin can be noted in states of hypokalemia, hypomagnesemia, & hypercalcemia which make establishment of the true therapeutic concentration of digoxin difficult.

Specimen

Patient Preparation: No special patient preparation is required.

Serum or plasma (EDTA, citrate, oxalate, or heparin) specimens may be used with the Stratus Digoxin method. If serum samples are used collect blood & allow to clot. If plasma samples are used, collect blood in a tube containing an appropriate anticoagulant. Blood samples should be drawn at least 5-6 hours after an oral dose of digoxin since valid interpretation requires that full drug distribution equilibrium be attained between plasma & myocardium. Serum & plasma samples are stable for one week when stored at 2-8 C. Samples should not be repetitively frozen & thawed prior to testing. If shipment is required, use dry ice.

Notes

Samples with levels of Digoxin greater than 4.0 ng/mL should be diluted with a normal human serum sample that has previously been evaluated & is known to be 0 (zero) for the Digoxin, & then reassayed.

Specimens reading less than 0.3 ng/mL should be reported as <0.3 ng/mL.

More general terms

• digoxin in body fluid
• therapeutic drug measurement

More specific terms

• digoxin free in serum/plasma

Additional terms

• digoxin (Lanoxin, Lanoxicaps, Digitek)