Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock.
Acetaminophen
Paracetamol
Personalization
Pharmacogenetic
Pharmacogenomic
Sepsis
Septic shock
Journal
BMC anesthesiology
ISSN: 1471-2253
Titre abrégé: BMC Anesthesiol
Pays: England
ID NLM: 100968535
Informations de publication
Date de publication:
16 02 2023
16 02 2023
Historique:
received:
03
10
2022
accepted:
10
02
2023
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
22
2
2023
Statut:
epublish
Résumé
Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. NCT02750163.
Sections du résumé
BACKGROUND
Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient.
METHODS
Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters.
RESULTS
8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes.
CONCLUSIONS
Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result.
TRIAL REGISTRATION
NCT02750163.
Identifiants
pubmed: 36797680
doi: 10.1186/s12871-023-02018-y
pii: 10.1186/s12871-023-02018-y
pmc: PMC9933278
doi:
Substances chimiques
Acetaminophen
362O9ITL9D
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A5 protein, human
EC 1.14.14.1
Banques de données
ClinicalTrials.gov
['NCT02750163']
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Informations de copyright
© 2023. The Author(s).
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