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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
  1. Mara Aparecida Maricato Poma1,2,
  2. Howard Lopes Ribeiro Junior1,3,4,5,
  3. Eugênio Araújo Costa6,
  4. Carlos Roberto Koscky Paier1,4,
  5. Laís Lacerda Brasil1,
  6. Luína Benevides Lima1,
  7. Livia Maria Soares Nobre1,
  8. Tayales Tavares Leite1,
  9. Roberto César Pereira Lima-Júnior1,2,5,
  10. Ana Rosa Pinto Quidute1,2,6,
  11. Maria Elisabete Amaral de Moraes1,2,
  12. Manoel Odorico de Moraes Filho1,2
  1. 1Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceará, Brazil
  2. 2Post-Graduate Program in Pharmacology, Federal University of Ceara, Fortaleza, Ceará, Brazil
  3. 3Molecular Oncology Research Center, Hospital de Câncer de Barretos, Barretos, São Paulo, Brazil
  4. 4Post-Graduate Program in Translational Medicine, Federal University of Ceara, Fortaleza, Ceará, Brazil
  5. 5Post-Graduate Program in Pathology, Federal University of Ceara, Fortaleza, Ceará, Brazil
  6. 6Post-Graduate Program in Medical-Surgical Sciences, Federal University of Ceara, Fortaleza, Ceará, Brazil
  1. Correspondence to Dr Howard Lopes Ribeiro Junior, Center for Research and Drug Development (NPDM). Cancer Cytogenomics Laboratory, Federal University of Ceara, Fortaleza, Ceará, Brazil; howard{at}ufc.br

Abstract

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
  • genetics

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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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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Footnotes

  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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