Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

Abstract Background Acetaminophen hepatotoxicity is thought to be primarily caused by formation of the specific reactive metabolite N‐acetyl‐para‐benzo‐quinone imine (NAPQI). Malnourished individuals are at increased risk of acetaminophen‐related hepatotoxicity. We report a case of low acetaminophen...

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Autores principales:	Daan Zillen, Kris L. L. Movig, Gert Kant, Joost B. Masselink, Paola Mian
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	acetaminophen eating disorders fasting glutathione hepatotoxicity metabolism Medicine R Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f3eaae8c5ba54ab6988fb92bf2126695
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spelling	oai:doaj.org-article:f3eaae8c5ba54ab6988fb92bf21266952021-12-01T06:36:08ZImpact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity2050-090410.1002/ccr3.4611https://doaj.org/article/f3eaae8c5ba54ab6988fb92bf21266952021-11-01T00:00:00Zhttps://doi.org/10.1002/ccr3.4611https://doaj.org/toc/2050-0904Abstract Background Acetaminophen hepatotoxicity is thought to be primarily caused by formation of the specific reactive metabolite N‐acetyl‐para‐benzo‐quinone imine (NAPQI). Malnourished individuals are at increased risk of acetaminophen‐related hepatotoxicity. We report a case of low acetaminophen clearance in a severely underweight young woman, and elaborate on the possible effects of malnutrition on the total clearance of acetaminophen as well as on the separate contributions of the different metabolic pathways. Case report An 18‐year‐old Caucasian woman weighing 43 kg with a history of eating disorder‐related hospital admissions presented at the emergency department after having ingested 33 tablets of acetaminophen 500 mg two hours earlier. She then received intravenous N‐acetylcysteine for 33 h. Nine hours after ingestion, the acetaminophen elimination half‐life (t½) was estimated to be >100 h. Discussion While decreased total acetaminophen clearance (twofold) due to malnutrition has been reported in literature, the extremely low clearance in this specific patient cannot be explained. Malnourished individuals generally have reduced antioxidant reserves, coinciding with a shift in metabolic routes toward oxidative metabolism. This may result in increased formation of NAPQI and reduced neutralizing capacity, thereby increasing the risk of acetaminophen‐induced hepatotoxicity. Evidence for this observation can be found in animal and to a lesser extent in human studies.Daan ZillenKris L. L. MovigGert KantJoost B. MasselinkPaola MianWileyarticleacetaminopheneating disordersfastingglutathionehepatotoxicitymetabolismMedicineRMedicine (General)R5-920ENClinical Case Reports, Vol 9, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acetaminophen eating disorders fasting glutathione hepatotoxicity metabolism Medicine R Medicine (General) R5-920
spellingShingle	acetaminophen eating disorders fasting glutathione hepatotoxicity metabolism Medicine R Medicine (General) R5-920 Daan Zillen Kris L. L. Movig Gert Kant Joost B. Masselink Paola Mian Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
description	Abstract Background Acetaminophen hepatotoxicity is thought to be primarily caused by formation of the specific reactive metabolite N‐acetyl‐para‐benzo‐quinone imine (NAPQI). Malnourished individuals are at increased risk of acetaminophen‐related hepatotoxicity. We report a case of low acetaminophen clearance in a severely underweight young woman, and elaborate on the possible effects of malnutrition on the total clearance of acetaminophen as well as on the separate contributions of the different metabolic pathways. Case report An 18‐year‐old Caucasian woman weighing 43 kg with a history of eating disorder‐related hospital admissions presented at the emergency department after having ingested 33 tablets of acetaminophen 500 mg two hours earlier. She then received intravenous N‐acetylcysteine for 33 h. Nine hours after ingestion, the acetaminophen elimination half‐life (t½) was estimated to be >100 h. Discussion While decreased total acetaminophen clearance (twofold) due to malnutrition has been reported in literature, the extremely low clearance in this specific patient cannot be explained. Malnourished individuals generally have reduced antioxidant reserves, coinciding with a shift in metabolic routes toward oxidative metabolism. This may result in increased formation of NAPQI and reduced neutralizing capacity, thereby increasing the risk of acetaminophen‐induced hepatotoxicity. Evidence for this observation can be found in animal and to a lesser extent in human studies.
format	article
author	Daan Zillen Kris L. L. Movig Gert Kant Joost B. Masselink Paola Mian
author_facet	Daan Zillen Kris L. L. Movig Gert Kant Joost B. Masselink Paola Mian
author_sort	Daan Zillen
title	Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
title_short	Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
title_full	Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
title_fullStr	Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
title_full_unstemmed	Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
title_sort	impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f3eaae8c5ba54ab6988fb92bf2126695
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Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

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