dc.contributor.author | Lao, Yvonne Elisabeth | |
dc.contributor.author | Molden, Espen | |
dc.contributor.author | Kringen, Marianne K. | |
dc.contributor.author | Annexstad, Ellen Johanne | |
dc.contributor.author | Sæverud, Håvard Andreassen | |
dc.contributor.author | Jacobsen, Dag | |
dc.contributor.author | Hovda, Knut Erik | |
dc.date.accessioned | 2020-11-09T08:12:21Z | |
dc.date.accessioned | 2021-02-10T10:29:57Z | |
dc.date.available | 2020-11-09T08:12:21Z | |
dc.date.available | 2021-02-10T10:29:57Z | |
dc.date.issued | 2020-01-24 | |
dc.identifier.citation | Lao Y, Molden, Kringen, Annexstad, Sæverud, Jacobsen, Hovda. Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes. Basic & Clinical Pharmacology & Toxicology. 2020;127(1):47-51 | en |
dc.identifier.issn | 1742-7835 | |
dc.identifier.issn | 1742-7843 | |
dc.identifier.uri | https://hdl.handle.net/10642/9496 | |
dc.description.abstract | Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes
may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after
therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where
pharmacogenetic screening was conducted.
This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given
over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening
showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the
formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had
decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to
NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI
may add to the risk of toxicity.
This case may indicate that pharmacogenetic variability is of potential relevance for the risk of
paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should
investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of
hepatotoxicity in these patients at therapeutic doses of paracetamol, and hence provide information for
selection of analgesic treatment. | en |
dc.language.iso | en | en |
dc.publisher | Wiley | en |
dc.relation.ispartofseries | Basic & Clinical Pharmacology & Toxicology;Volume 127, Issue 1, July 2020 | |
dc.rights | This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:
10.1111/BCPT.13389 | en |
dc.subject | Paracetamol | en |
dc.subject | Hepatotoxicity | en |
dc.subject | Pharmacogenetic profiles | en |
dc.subject | Neuromuscular diseases | en |
dc.subject | Duchenne muscular dystrophy | en |
dc.title | Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes | en |
dc.type | Journal article | en |
dc.type | Peer reviewed | en |
dc.date.updated | 2020-11-09T08:12:21Z | |
dc.description.version | acceptedVersion | en |
dc.identifier.doi | https://doi.org/10.1111/bcpt.13389 | |
dc.identifier.cristin | 1840631 | |
dc.source.journal | Basic & Clinical Pharmacology & Toxicology | |