Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2022-12-01 DOI:10.1515/dmpt-2021-0222

Dmitry A Sychev, Tatiana E Morozova, Dmitry A Shatskiy, Nadezhda V Shikh, Evgeniya V Shikh, Tatiana B Andrushchyshina, Maria V Lukina, Anastasia A Kachanova, Zhannet A Sozaeva, Sherzod P Abdullaev, Natalia P Denisenko, Kristina A Ryzhikova

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引用次数: 0

Abstract

Objectives: Patients undergoing cardiac surgery develop post-sternotomy pain syndrome. The aim of this study was evaluation of the influence of CYP2C9, PTGS-1 and PTGS-2 genes polymorphisms on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Methods: The study included 90 patients undergoing cardiac surgery. A real-time polymerase chain reaction was used for the detection of single nucleotide polymorphisms (SNP). Pain intensity was measured by the Numeric Rating Scale (NRS). Dyspeptic symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Acute kidney injury (AKI) was determined by Kidney Disease Improving Global Outcomes criteria.

Results: Pain intensity by the NRS score was significantly higher in patients with CYP2C9*3 АA genotype compared to АC genotype: 7 [1,10] and 6 [2,7] (p=0.003); 7 [1,10] and 6 [2,7] (p=0.04); 6 [0; 10] and 5 [2,6] (p=0.04); 5 [0; 8] and 3 [0; 8] (p=0.02), on days 1, 2, 3 and 5 in the postoperative period, respectively. GSRS score was higher in patients with CYP2C9*2 CT genotype compared to CС genotype: 19 [15; 42] and 18 [15,36] (p=0.04), respectively. There were no significant differences in the pain intensity, dyspepsia severity and AKI frequency in patients with homozygous and heterozygous genotypes for PTGS-1 rs10306135, PTGS-1 rs12353214, PTGS-2 rs20417.

Conclusions: CYP2C9*3 and CYP2C9*2 gene polymorphisms may affect efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

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CYP2C9、PTGS-1和PTGS-2基因多态性对酮洛芬术后镇痛疗效和安全性的影响

目的:心脏手术患者出现胸骨切开术后疼痛综合征。本研究旨在评价CYP2C9、PTGS-1和PTGS-2基因多态性对冠心病患者心脏手术后酮洛芬镇痛的疗效和安全性的影响。方法:本研究纳入90例心脏手术患者。采用实时聚合酶链反应检测单核苷酸多态性(SNP)。采用数值评定量表(NRS)测量疼痛强度。使用胃肠症状评定量表(GSRS)评估消化不良症状。急性肾损伤(AKI)由肾脏疾病改善全球结局标准确定。结果:CYP2C9*3 АA基因型患者NRS评分疼痛强度显著高于АC基因型患者:7[1,10]和6 [2,7](p=0.003);7[1,10]和6 [2,7](p=0.04);6 (0;10]和5 [2,6](p=0.04);5 (0;8]和3 [0;[8] (p=0.02)，分别于术后第1、2、3、5天。CYP2C9*2 CT基因型患者GSRS评分高于CС基因型患者:19 [15;[42]和[15,36](p=0.04)。PTGS-1 rs10306135、PTGS-1 rs12353214、PTGS-2 rs20417基因型纯合子和杂合子患者的疼痛强度、消化不良严重程度和AKI频率无显著差异。结论:CYP2C9*3、CYP2C9*2基因多态性可能影响冠心病患者心脏手术后酮洛芬镇痛的疗效和安全性。

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来源期刊

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.