CYP2D6基因多态性对汉族肾切除患者曲马多术后镇痛的影响。
Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in Han nationality nephrectomy patients.
作者信息
Dong Hong, Lu Shu-Jun, Zhang Rui, Liu Dong-Dong, Zhang Yan-Zhuo, Song Chun-Yu
机构信息
Department of Anesthesiology, China and Heilongjiang Key Laboratory for Anesthesia and Critical Care, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xue-fu Street, Nangang District, Harbin, 150081, Heilonjiang, China.
出版信息
Eur J Clin Pharmacol. 2015 Jun;71(6):681-686. doi: 10.1007/s00228-015-1857-4. Epub 2015 May 8.
OBJECTIVE
Tramadol is a synthetic opioid which has analgesic efficacy in the postoperative pain. It is metabolized by polymorphic enzyme cytochrome P450 (CYP2D6). Patients with different CYP2D6 genotypes would have different responses to tramadol in pain relief. The CYP2D610 allele is the most common allele in a Chinese population. The aim of this study was to evaluate whether the different CYP2D610 genotypes have an effect on the postoperative tramadol analgesia in the Chinese population after elective nephrectomy.
METHODS
One hundred and twenty patients after performed elective nephrectomy were enrolled in this study after being approved by the local Ethics Committee. The patients were given patient-controlled analgesia (PCA) which included 10 mg/ml tramadol after receiving a loading dose of 100 mg tramadol and 1 mg granisetron intravenously. Blood samples were collected after induction of anesthesia. The CYP2D610 polymorphism was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). According to the results, the patients were divided into three groups (CYP2D61/1, n = 33; CYP2D61/10, n = 28; CYP2D610/*10, n = 50). The total consumption of tramadol, visual analogue scale (VAS) score, and PCA control times among the three genotype groups for 2, 4, 24, 48, and 72 h after operation were compared.
RESULTS
Nine out of 120 patients were dropped out of the study; 111 patients completed the study. The frequency of CYP2D610 allele was 57.7%. The demographic data among the three groups were comparable. The consumption of tramadol, patient self-control times of pump, and VAS score in CYP2D610/10 group were significantly higher than that in CYP2D61/1 or CYP2D61/*10 group at 2 and 4 h (P < 0.05), while it did not differ between CYP2D6*1/*1 and CYP2D6*1/*10 group (P > 0.05). There was no difference in the incidence of nausea and vomiting among the three groups (P > 0.05). No sever apnea was recorded in these groups.
CONCLUSIONS
Different CYP2D6*10 genotypes have an influence on the analgesic effect of tramadol in Han nationality patients after elective nephrectomy.
目的
曲马多是一种合成阿片类药物，对术后疼痛具有镇痛效果。它由多态性酶细胞色素P450（CYP2D6）代谢。不同CYP2D6基因型的患者对曲马多的镇痛反应可能不同。CYP2D610等位基因是中国人群中最常见的等位基因。本研究旨在评估不同的CYP2D610基因型对中国人群择期肾切除术后曲马多镇痛效果的影响。
方法
120例择期肾切除术后患者经当地伦理委员会批准后纳入本研究。患者在静脉注射100mg曲马多负荷剂量和1mg格拉司琼后，接受包含10mg/ml曲马多的患者自控镇痛（PCA）。麻醉诱导后采集血样。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析CYP2D610基因多态性。根据结果，将患者分为三组（CYP2D61/1，n = 33；CYP2D61/10，n = 28；CYP2D610/*10，n = 50）。比较三组基因型患者术后2、4、24、48和72小时曲马多的总消耗量、视觉模拟评分（VAS）及PCA控制次数。
结果
120例患者中有9例退出研究；111例患者完成研究。CYP2D610等位基因频率为57.7%。三组间的人口统计学数据具有可比性。CYP2D610/10组在术后2和4小时的曲马多消耗量、患者自控泵次数及VAS评分显著高于CYP2D61/1组或CYP2D61/*10组（P < 0.05），而CYP2D6*1/*1组和CYP2D6*1/*10组之间无差异（P > 0.05）。三组间恶心呕吐发生率无差异（P > 0.05）。这些组中未记录到严重呼吸暂停。
结论
不同的CYP2D6*10基因型对汉族患者择期肾切除术后曲马多的镇痛效果有影响。
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