Open AccessThe Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers
Author(s) -
A. Min Kang,
Angela Padilla-Jones,
Erik S Fisher,
Jephte Y. Akakpo,
Hartmut Jaeschke,
Barry H. Rumack,
Richard Gerkin,
Steven C. Curry
Publication year - 2019
Publication title -
journal of medical toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.534
H-Index - 49
eISSN - 1937-6995
pISSN - 1556-9039
DOI - 10.1007/s13181-019-00740-z
Subject(s) - acetaminophen , cyp2e1 , pharmacology , metabolite , cyp1a2 , metabolism , medicine , oxidative phosphorylation , glutathione , pharmacokinetics , drug metabolism , urine , liver injury , chemistry , cytochrome p450 , biochemistry , drug , enzyme
Acetaminophen (APAP) is commonly ingested in both accidental and suicidal overdose. Oxidative metabolism by cytochrome P450 2E1 (CYP2E1) produces the hepatotoxic metabolite, N-acetyl-p-benzoquinone imine. CYP2E1 inhibition using 4-methylpyrazole (4-MP) has been shown to prevent APAP-induced liver injury in mice and human hepatocytes. This study was conducted to assess the effect of 4-MP on APAP metabolism in humans.