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Unit Code 4901:
Acetaminophen, Plasma, NIH Units

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Useful For

-  Monitoring toxicity in overdose cases

-  Serum concentration and half-life are the only way to assess

   degree of intoxication in early stages since other liver function

   studies (e.g., bilirubin, liver function enzymes) will not show

   clinically significant increases until after tissue damage has

   occurred, at which point therapy is ineffective.

Clinical Information

-  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: N-Acetyl-Imidoquinone) 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.

Reference Values

Therapeutic concentration:  <50 mg/L

Toxic concentration:  > or = 120 mg/L

Half-life:  <4 h

Toxic half-life:  >4 h

 

The toxic level is dependent on half-life. When the half-life is 4 h,

hepatotoxicity generally is not seen until the concentration is greater

or equal to 120 mg/L. The level at which toxicity occurs decreases

with increasing half-lives until it is encountered at values as low as

50 mg/L when the half-life reaches 12 h.

Interpretation

-  Therapeutic concentration:  <50 mg/L

-  Normal half-life: <4 hours

- Toxic concentration:  120 mg/L

-  Toxic half-life:  >4 hours

-  The toxic level is dependent on half-life.

      -  When the half-life is 4 hours, hepatotoxicity generally will not

          occur unless the concentration is 120 mg/L.

      -  The level at which toxicity occurs decreases with increasing

          half-life until it is encountered at values as low as 50 mg/L

          when the half-life reaches 12 hours.

Cautions

-  First specimen should be collected no sooner than 2 hours

   post-ingestions.

-  For half-life determination, collect two specimens at least 4 hours

   apart and note the exact time of each collection. Half-life can be

   calculated from the concentrations and the time interval.

Clinical Reference

-  Rumack BH, Peterson RG:  Acetaminophen overdose: incidence,

   diagnosis, and management in 416 patients.  Pediatrics 62:898-903,

   1978

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