April 25, 2017
Acetaminophen toxicity is a result of the formation of a reactive intermediate N-acetyl-p-benzoquinonimine (NAPQI), the product of a minor pathway involved in the metabolism of acetaminophen. At therapeutic doses, the majority of acetaminophen metabolism occurs via glucuronidation and sulfation to nontoxic metabolites. In overdose, the nontoxic routes of metabolism become saturated and the metabolism of acetaminophen to NAPQI becomes a major metabolic pathway. The formation of NAPQI occurs primarily via oxidation by hepatic CYP2E1 and, to a lesser extent, by CYP3A4, CYP2A6, and CYP1A2. A fraction of the total NAPQI may be a result of renal CYP2E1 metabolism.