N-Hydroxyacetaminophen: a postulated toxic metabolite of acetaminophen
- 1 August 1981
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 24 (8) , 988-993
- https://doi.org/10.1021/jm00140a014
Abstract
Decomposition of N-hydroxyacetaminophen occurred via an initial 1st-order dehydration step to N-acetyl-p-benzoquinonimine with a rate constant at pH 7.6 of 8.66 .times. 10-3 min-1 and a half-life of 80 min. This was followed by a complex reaction between the quinone imine and the N-hydroxy compound to yield p-nitrosophenol and acetaminophen. Glucuronide and sulfate conjugates of N-hydroxyacetaminophen were observed as urinary metabolites of N-hydroxyacetaminophen. No N-hydroxylated metabolites were found among metabolites of acetaminophen. N-hydroxyacetaminophen was not a metabolite of acetaminophen. Hepatotoxicity and nephrotoxicity of acetaminophen in rats and mice was mediated by a direct oxidation of acetaminophen to the toxic reactive intermediate N-acetyl-p-benzoquinonimine by the cytochrome P-450 dependent mixed-function oxidase system.This publication has 5 references indexed in Scilit:
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