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. 2015 Aug;25(8):416-26.
doi: 10.1097/FPC.0000000000000150.

PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses

Liudmila L Mazaleuskaya  1 , Katrin Sangkuhl, Caroline F Thorn, Garret A FitzGerald, Russ B Altman, Teri E Klein
Affiliations

PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses

Liudmila L Mazaleuskaya et al. Pharmacogenet Genomics. 2015 Aug.
No abstract available

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Conflict of interest statement

Conflicts of interest

RBA and TEK are stockholders in Personalis Inc. The other authors declare no conflicts of interest. GAF is the McNeil Professor of Translational Medicine and Therapeutics.

Figures

Figure 1
Figure 1
Metabolism and transport of acetaminophen in the liver at therapeutic doses. Glucuronidation is the main pathway of acetaminophen metabolism, followed by sulfation and a minor contribution from the oxidation route. Oxidation by CYP isozymes yields a reactive metabolite NAPQI that is detoxified by the glutathione pathway. Phenobarbital and phenytoin inhibit acetaminophen glucuronidation, while ethanol and isoniazid potentiate acetaminophen oxidation. Enzymes playing a major role in the corresponding pathway are denoted with a star. APAP, acetaminophen; APAP gluc, acetaminophen glucuronide; APAP-cys, acetaminophen cysteine; NAPQI, N-acetyl-p-benzoquinone imine. A fully interactive version is available online at http://www.pharmgkb.org/pathway/PA165986279.
Figure 2
Figure 2
Metabolism and transport of acetaminophen in the liver at highly toxic doses. After ingestion of highly toxic doses of acetaminophen, glucuronidation and sulfation pathways get saturated and higher portion of the drug gets oxidized and excreted unchanged. Excess NAPQI depletes glutathione stores causing liver injury. Administration of NAC provides an exogenous source of glutathione that will neutralize NAPQI and prevent further hepatotoxicity. Enzymes playing a major role in the corresponding pathway are denoted with a star. APAP, acetaminophen; APAP gluc, acetaminophen glucuronide; APAP-cys, acetaminophen cysteine; NAPQI, N-acetyl-p-benzoquinone imine; NAC, N-acetylcysteine. A fully interactive version is available online at http://www.pharmgkb.org/pathway/PA166117881.
See this image and copyright information in PMC

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