Clinical Aspects

Why Knowledge of Accurate Acetaminophen Protein Adduct Levels is Important

Acetaminophen is the most widely used analgesic agent in the US and Europe, representing 23% of all prescription and OTC drugs in the US.

When used as labeled, it is generally safe. However, both the ubiquity of the Acetaminophen and its narrow therapeutic index – defined as the ratio of the dose that produces toxicity to the dose that produces a clinically desired response – creates the potential for serious harm from intentional and unintentional overdoses.

APAP Metabolic Pathway

Clinical Implications

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Accurate knowledge of acetaminophen protein adduct levels are useful in:

  • Suspected Acetaminophen overdose
  • Liver toxicity of unknown etiology
  • Suspected exposure to multiple over-the-counter medications containing acetaminophen
  • Suspected undocumented use of Acetaminophen
  • Suspected overuse of combination narcotic drugs that contain Acetaminophen
  • Compromised subjects in which increased susceptibility to Acetaminophen is suspected

Behind the Science

Excessive exposure to Acetaminophen overwhelms normal detoxification mechanisms and can cause serious liver toxicity that is mediated by the reactive metabolite N-acetyl-p-benzoquinone imine which binds covalently to protein primarily as 3-(cysteine-S-yl) acetaminophen (acetaminophen protein adduct).

Acetaminophen liver injury, defined as alanine aminotransferase elevation in a patient suspected to have Acetaminophen overdose, is highly correlated with the elevation of Acetaminophen Protein Adducts in patient serum.

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