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CYP2D6 同工酶和 ABCB1 基因多态性与行腹腔镜胆囊切除术的女性术后恶心和呕吐的相关性:一项随机试验。

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial.

机构信息

Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, RJ, Brazil.

Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, RJ, Brazil.

出版信息

Braz J Anesthesiol. 2024 May-Jun;74(3):744423. doi: 10.1016/j.bjane.2023.02.002. Epub 2023 Feb 23.

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.

REGISTER

ClinicalTrials.gov.

摘要

简介

术后恶心和呕吐仍然是一种常见的并发症。5-羟色胺受体拮抗剂在临床上常用于止吐预防。药物反应的个体间差异,包括单核苷酸多态性,与这些药物的药代动力学和药效学变化有关,可能导致治疗反应不佳。本研究旨在评估细胞色素 P450 2D6 同工酶和 ABCB1 基因多态性对使用昂丹司琼或帕洛诺司琼预防术后恶心和呕吐的频率的影响。

方法

一项纳入 82 名 60 岁或以上接受腹腔镜胆囊切除术的女性的随机、双盲临床试验。患者被随机分配接受昂丹司琼或帕洛诺司琼用于预防术后恶心和呕吐。从唾液中提取 DNA。通过实时聚合酶链反应分析遗传多态性。分析了以下多态性:rs3892097 C/T、rs1128503 A/G、rs16947 A/G、rs1065852 A/G、rs1045642 A/G、rs2032582 C/A 和 rs20325821 C/A。

结果

总体而言,22.5%的患者出现呕吐,57.5%的患者出现严重恶心。在帕洛诺司琼组中,rs16947 A/G 的 GG 基因型(rs16947 A/G)的患者出现更严重的恶心(p=0.043)。在昂丹司琼组中,rs16947 A/G 的 AA 基因型(rs16947 A/G)的患者出现轻度恶心(p=0.034),rs1065852 A/G 的 AA 基因型(rs1065852 A/G)的患者出现更多的呕吐(p=0.034)。

结论

在腹腔镜胆囊切除术中,使用昂丹司琼时存在 AA 基因型(rs16947 A/G)和 AA 基因型(rs1065852 A/G)时,抗呕吐反应较低,使用帕洛诺司琼时存在 GG 基因型(rs16947 A/G)时,治疗反应较低。

登记

ClinicalTrials.gov。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68b6/11148501/7babd67e7e11/gr1.jpg

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