N-acetyl-p-benzoquinone imine NAPQI

FIGURE 7.11 Proposed metabolic activation of paracetamol to a toxic, reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI). This can react with glutathione (GSH) to form a conjugate or with tissue proteins,... 

NAP Neutrophil-activating peptide NAPQI N-acetyl-p-benzoquinone imine... 

Acetaminophen (APAP, N-acetyl-p-aminophenol, paracetamol) is a widely used over-the-counter analgesic. At erapeutic doses it is a safe drug. However, at high doses it may produce severe hepatic necrosis and has also been reported in some individuals to be nephrotoxic (1-3). Available evidence indicates that acetaminophen hepatotoxicity is not a result of the parent compound but is mediated by a reactive metabolite N-acetyl-g-benzoquinone imine (NAPQI). This metabolite is the two-electron oxidation product of acetaminophen and is formed by the microsomal cytochrome P-450 mixed function oxidase system (4-8). Following a therapeutic dose of acetaminophen the reactive metabolite is detoxified Current address National Institutes of Health, Bethesda, MD 20892 Current address Rohm and Haas Company, Spring House, PA 19477... 

ALT alanine aminotransferase AST aspartate aminotransferase CYP cytochrome P450 liver enzyme system NAPQI V-acetyl-p-benzoquinone imine NAT2 N-acetyltransferase 2 genotype... 

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