Background The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.98T>C, rs72551330) polymorphisms on the pharmacokinetics of single-drug propofol in adult patients undergoing intravenous sedation.
Methods In this prospective clinical study, a total of 124 patients undergoing anaesthesia with propofol, as a single drug, were evaluated when undergoing colonoscopy procedure. Clinical variables were obtained from the patient’s anamnesis prior to performing the anaesthetic procedure, in the moment of the patient’s loss of consciousness, during the colonoscopy exam (recorded every 5 min) and in the awakening time.
Results Polymorphic genotypes for the rs3745274 and rs1057910 polymorphisms were associated with bispectral index, target-controlled infusion (TCI)/effector concentration of propofol and TCI/plasma concentration of propofol values. Based on multivariate analysis, it was observed that weight, age, surgery time, systolic blood pressure and the rs1057910 polymorphism corresponded to predictive values for the dose of propofol used. Weight (B=4.807±0.897), age (B=1.834±0.834) and duration of surgery (B=8.164±1.624) corresponded to factors associated with increased propofol dose, while systolic blood pressure (B=−1.892±0.679) and the genotypes (AA vs CA) of the single nucleotide polymorphism (SNP) rs1057910 CYPP2C9 gene (B=−74.161±26.820) decreased the total dose of propofol used.
Conclusion We concluded that the rs1057910 and rs3745274 polymorphisms affect the metabolism of propofol in patients exclusively submitted to this drug. Thus, the knowledge of the polymorphic genotypes of the CYPP2C9 and CYB2B6 genes may be predictive of different metabolising phenotypes, suggesting expected behaviours of BIS parameter in the anaesthetic procedure, which contributes to safer monitoring by anaesthesiologists during the clinical intervention.
- adult anaesthesia
- molecular biology
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.
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Contributors MAMP, HLRJ and CRKP had the conceptual idea for the article. The literature search was performed by MAMP and HLRJ. The first draft of the manuscript was written by MAMP and HLRJ, and all authors commented on subsequent versions of manuscript and provided a critical revision for important intellectual content. HLRJ is the guarantor of this article. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note This study is part of the requirements for a PhD degree presented by Dr Mara Aparecida Maricato Poma at the Post Graduation Program in Medical-Surgical Sciences, Federal University of Ceara.
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