Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (899 page)

   Limitations

   Draw blood 6–8 hours (or 8–24 hours) after last oral dose after steady state has been achieved in 1–2 weeks.

   Pediatric toxic concentration may be higher; therapeutic index is very low (i.e., small difference between therapeutic and toxic blood concentration). However, approximately 10% of patients have serum concentration of 2–4 ng/mL without evidence of toxicity. On a dose of 0.25 mg/day, mean serum concentration is 1.2 ± 0.4 ng/mL; on a dose of 0.5 mg/day, mean serum concentration is 1.5 ± 0.4 ng/mL. A
Digitalis
leaf dose of 0.1 g/day produces the same serum concentration as 0.1 mg/day of crystalline digitoxin. There is ECG evidence of toxicity in one third to two thirds of patients, with no symptoms or signs.

   False low results may be due to spironolactone.

   Endogenous digoxin-like substances may produce positive test results in persons who have not received the drug, especially in

   Uremia.

   Severe agonal states and postmortem—therefore, a high postmortem concentration may not have been high before death and a normal postmortem concentration suggests that the antemortem concentration was not toxic.

   Because most methods measure both endogenous digoxin-like substances and inactive metabolites of digoxin, therapeutic monitoring should mostly be used to assess patient compliance and to confirm drug toxicity.

   Tests: bioassay, Na
⁺
/K
⁺
-ATPase receptor assay, colorimetry, fluorometry, HPLC, GC, enzyme assay, immunoassay, and LC/MS.

   Immunoassay is the most widely used methodology: RIA, FPIA, EIA, and chemiluminescence.

   Confounders in analysis-low concentrations, steroid-like nucleus, endogenous digoxin-like immunoreactive factors (observed in patients with renal failure, liver disease, MI, newborns, pregnancy, hypertension, strenuous exercise, volume expansion), digoxin metabolites, presence of antidote (Fab).

   Immunoassays exhibit <5% cross-reactivity with digitoxin and digoxigenin, and 80–100% with the metabolites digoxigenin bis- and monodigitoxoside.