Serum Digoxin Concentration Test
The test used to check digoxin levels in the blood is a serum digoxin concentration measurement, typically performed using immunoassay methods such as fluorescence polarization immunoassay (FPIA), enzyme immunoassay (EIA), or chemiluminescence immunoassay. 1, 2
Timing of Blood Sample Collection
Critical timing requirements must be followed to obtain accurate results:
- Sample collection must occur just before the next scheduled dose (trough level) 1
- If trough sampling is not possible, wait at least 6-8 hours after the last dose, regardless of administration route 1
- On once-daily dosing, concentrations will be 10-25% lower at 24 hours versus 8 hours post-dose, depending on renal function 1
- On twice-daily dosing, minimal differences occur between 8 and 12 hours post-dose 1
Therapeutic Range and Interpretation
The recommended therapeutic range is 0.5-1.0 ng/mL according to the American Heart Association, with optimal clinical benefit and minimal toxicity risk. 3
- The European Society of Cardiology recommends a slightly wider range of 0.6-1.2 ng/mL for chronic therapy 3
- The FDA label indicates that two-thirds of adequately digitalized adults have concentrations of 0.8-2.0 ng/mL, though this upper limit is now considered too high 1
- Overt toxicity is commonly associated with levels >2.0 ng/mL 4, 5, 3
- However, one-third of patients with clinical toxicity have levels <2.0 ng/mL 1
When to Order the Test
Monitor serum digoxin levels in these specific situations:
- Early during chronic therapy, especially in patients with renal impairment 3
- When adding medications that increase digoxin levels (amiodarone, clarithromycin, erythromycin, itraconazole, cyclosporine, verapamil, quinidine, propafenone, dronedarone) 5, 3
- When signs or symptoms of toxicity appear: confusion, nausea, anorexia, visual disturbances (blurred or yellow vision), or cardiac arrhythmias 5, 3
- Periodically to assess serum electrolytes and renal function 1
Available Testing Methods
Multiple immunoassay platforms are available, each with specific advantages: 2
- Fluorescence polarization immunoassay (FPIA): Sensitive and convenient, commonly used in automated analyzers 2, 6
- Enzyme immunoassay (EIA): Good specificity 2
- Chemiluminescence immunoassay: Excellent sensitivity and stability 2
- Radioimmunoassay: Low cost but less commonly used now 2
- HPLC-MS-MS: High resolution and excellent specificity, but not routinely available 2
Critical Interpretation Pitfalls
Always interpret serum digoxin concentration in the full clinical context—never use an isolated measurement alone to adjust dosing. 1
Factors that cause falsely elevated or interfering results:
- Endogenous digoxin-like immunoreactive substances (DLIS) in volume-expanded patients 7
- Spironolactone and potassium canrenoate 7
- Digoxin-specific Fab antibodies (Digibind) used in overdose treatment 7
- Chinese medicines such as Chan Su, Lu-Shen Wan, and oleander-containing preparations 7
Conditions causing increased sensitivity to digoxin despite "therapeutic" levels:
- Hypokalemia, hypomagnesemia, or hypothyroidism increase toxicity risk even at levels <2.0 ng/mL 4, 5, 3, 1
- Hypercalcemia predisposes to digitalis toxicity 1
- Cardiac amyloidosis: digoxin binds to amyloid fibrils, creating tissue reservoirs not reflected in serum levels—serum levels do not guarantee safety in these patients 8
- Renal impairment and advanced age increase toxicity risk 5, 1
Exercise transiently decreases serum digoxin concentration without changing clinical efficacy due to increased skeletal muscle binding. 1