CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial
Polimorfismos da isoenzima CYP2D6 e do gene ABCB1 associados a náuseas e vômitos pós-operatórios em mulheres submetidas à colecistectomia laparoscópica: um ensaio randomizado
Angela Henrique Silva Ribeiro, Estêvão Luiz Carvalho Braga, Nathalia de Araújo Gouveia Ferreira, Beni Olej, Nubia Verçosa, Leonardo dos Santos Antunes, Ismar Lima Cavalcanti
Abstract
Introduction
Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interindividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron.
Methods
A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A.
Results
Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the AA genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034).
Conclusion
A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy.
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Keywords
Resumo
Introdução
Náuseas e vômitos pós-operatórios ainda são uma complicação comum. Os antagonistas dos receptores de serotonina são comumente usados na prática clínica para profilaxia antiemética. Variações interindividuais na resposta aos medicamentos, incluindo polimorfismos de nucleotídeo único, estão relacionadas a alterações farmacocinéticas e farmacodinâmicas nesses medicamentos e podem levar a uma resposta terapêutica deficiente. Este estudo teve como objetivo avaliar a influência da isoenzima CYP2D6 e dos polimorfismos do gene ABCB1 na frequência de náuseas e vômitos pós-operatórios com uso de ondansetrona ou palonossetrom.
Métodos
Foi realizado um ensaio clínico randomizado, duplo-cego, incluindo 82 mulheres com 60 anos ou mais submetidas à colecistectomia laparoscópica. Os pacientes foram randomizados para receber ondansetrona ou palonossetrom para profilaxia de náuseas e vômitos no pós-operatório. O DNA foi extraído da saliva. Os polimorfismos genéticos foram analisados por reação em cadeia da polimerase em tempo real. Foram analisados os seguintes polimorfismos: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A e rs20325821 C/A.
Resultados
No geral, vômitos e náuseas graves ocorreram em 22,5% e 57,5% dos pacientes, respectivamente. No grupo palonossetrom, os pacientes com genótipo GG (rs16947 A/G) apresentaram náuseas mais intensas (p = 0,043). No grupo ondansetrona, pacientes com genótipo AA (rs16947 A/G) apresentaram náusea leve (p = 0,034), e aqueles com genótipo AA (rs1065852 A/G) apresentaram mais vômitos (p = 0,034).
Conclusão
Uma baixa resposta antiemética foi observada com ondansetrona na presença do genótipo AA (rs16947 A/G) e do genótipo AA (rs1065852 A/G), e uma baixa resposta terapêutica foi encontrada com palonossetrom na presença do genótipo GG (rs16947 A/G) em colecistectomia laparoscópica.
Palavras-chave
References
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Submitted date:
09/11/2022
Accepted date:
02/13/2023
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