When the amount of NAPQI generated exceeds hepatic glutathione stores, NAPQI binds to cellular and mitochondrial proteins causing dysfunction.

After an acetaminophen overdose, a much larger amount of acetaminophen is oxidized by CYP2E1 resulting in elevated amounts of NAPQI. During appropriate use of acetaminophen at therapeutic doses, the small amount of NAPQI produced is readily detoxified by intracellular glutathione. In addition to these pathways, approximately 5% of an acetaminophen dose is metabolized by cytochrome P450 enzymes (mainly CYP2E1), which results in the formation of a highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Oxidative metabolism: At therapeutic doses, 95% of APAP is metabolized via glucuronidation and sulfation in the liver and eliminated from the body without resulting toxicity. Acetaminophen overdose can induce acute liver failure by a process that involves two processes: oxidative metabolism and amplification of oxidant stress. This is a persistent health problem because acetaminophen is widely available in the US market.

Acetaminophen overdose is the most common cause of drug-induced acute liver failure (ALF) in the US, accounting for 46% of all cases, which results in about 300-500 deaths annually. Unintentional and intentional overdoses occur and can cause serious hepatotoxicity. The maximal recommended therapeutic dose of 4 g per day is safe and is well tolerated. Why Should I Register and Submit Results?Īcetaminophen (N-acetyl-p-aminophenol, paracetamol) is a commonly used analgesic and antipyretic.

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