Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study

• Published in: Postgraduate medical journal 2023-05, Vol.99 (1170), p.286-295
• Main Authors: Poma, Mara Aparecida Maricato, Ribeiro Junior, Howard Lopes, Costa, Eugênio Araújo, Paier, Carlos Roberto Koscky, Brasil, Laís Lacerda, Lima, Luína Benevides, Nobre, Livia Maria Soares, Leite, Tayales Tavares, Lima-Júnior, Roberto César Pereira, Quidute, Ana Rosa Pinto, de Moraes, Maria Elisabete Amaral, Moraes Filho, Manoel Odorico de
• Format: Article
• Language: English
• Subjects: adult anaesthesia; genetics; molecular biology; Original research
• ISSN: 0032-5473; 1469-0756
• DOI: 10.1136/postgradmedj-2021-141375

BackgroundThe 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.MethodsIn 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.ResultsPolymorphic 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.ConclusionWe 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.