FIGURE 1.

Acetaminophen metabolism. At therapeutic doses, 90% of acetaminophen is metabolized to glucuronide and sulfate compounds and ultimately excreted via the renal system. Of the remaining acetaminophen, 50% is excreted unchanged in the urine, and the remainder is metabolized by the cytochrome P450 system; a hepatotoxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), is subsequently produced. Hepatic glutathione conjugates with NAPQI to produce nontoxic metabolites that are renally excreted. With a toxic ingestion of acetaminophen, the glucuronidation and sulfation pathways become overwhelmed, and glutathione stores diminish, resulting in hepatocyte necrosis due to NAPQI.