Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock

BMC Anesthesiology

Research

F. Gasparri¹  C. Scorcella¹  R. Domizi¹  A. Carsetti²  A. Donati²  C. D’angelo²  E. Damiani²  E. Adrario²  E. Casarotta²  P. Castaldo³  S. Amoroso³ 

[1] Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, via Conca 71, 60126, Torrette di Ancona, Italy;Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, via Conca 71, 60126, Torrette di Ancona, Italy;Department of Biomedical Sciences and Public Health, Università Politecnica Delle Marche, via Tronto 10/a, 60020, Torrette di Ancona, Italy;Department of Biomedical Sciences and Public Health, Università Politecnica Delle Marche, via Tronto 10/a, 60020, Torrette di Ancona, Italy;

关键词: Sepsis;    Septic shock;    Acetaminophen;    Paracetamol;    Personalization;    Pharmacogenetic;    Pharmacogenomic;   

DOI  :  10.1186/s12871-023-02018-y

 received in 2022-10-03, accepted in 2023-02-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPharmacogenetics 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.MethodsSecondary 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.Results8% 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.ConclusionsIdentifying 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 registrationNCT02750163.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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