The hepatotoxicity of acetaminophen originates from the metabolism of the drug in vivo. The main metabolic pathway of acetaminophen is sulfation and glucuronization. A small part of it is metabolized by cytochrome P450 enzyme to produce a highly active intermediate metabolite, namely n-acetyl-p-quinoline imine (NAPQI). This metabolite can be covalently bound with reduced glutathione, and then be detoxified and excreted through the kidney. Therefore, acetaminophen does not produce hepatotoxicity at the commonly used therapeutic dose. However, when taken in large doses, the original metabolism is saturated, glutathione is exhausted, and the excess NAPQI will be combined with hepatocyte protein to inhibit its activity, resulting in liver injury.<br>
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