Clinical and Interpretive

Serum concentration and half-life are the only way to assess degree of intoxication in early stages since other liver function studies (eg, bilirubin, liver function enzymes) will not show clinically significant increases until after tissue damage has occurred, at which point therapy is ineffective.

Acetaminophen (found in Anacin-3, Comtrex, Contac, Datril, Dristan, Excedrin, Nyquil, Sinutab, Tempera, Tylenol, Vanquish, and many others) is an analgesic, antipyretic drug lacking significant anti-inflammatory activity. It is metabolized by the liver with a normal elimination half-life of <4 hours. In normal therapeutic doses, a minor metabolite, possessing electrophilic alkylating activity, readily reacts with glutathione in the liver to yield a detoxified product. In overdose situations, liver glutathione is consumed and the toxic metabolite (postulated metabolite: benzoquinone) reacts with cellular proteins resulting in hepatotoxicity, characterized by centrilobular necrosis, and possible death, if untreated.N-acetylcysteine can substitute for glutathione and serves as an antidote.

Half-life: <4 hours
Toxic half-life: >4 hours

The toxic level is dependent on half-life. When the half-life is 4 hours, hepatotoxicity generally is not seen until the concentration is ≥120 mcg/mL. The level at which toxicity occurs decreases with increasing half-lives until it is encountered at values as low as 50 mcg/mL when the half-life reaches 12 hours.

For half-life determination, draw 2 specimens at least 4 hours apart and note the exact time of each draw. Half-life can be calculated from the concentrations and the time interval. First specimen should be drawn no sooner than 2 hours post-ingestion.