CYP3A4＊1G基因多态性对硬膜外注射左旋布比卡因药代动力学的影响  

Effect of CYP3A4＊1G genetic polymorphism on pharmacokinetics of levobupivacaine after epidural administration

作　　者：冉菊红[1] 王艳萍[1] 马民玉[1] 

机构地区：[1]郑州大学第一附属医院麻醉科,450052

出　　处：《中华麻醉学杂志》2017年第6期715-718,共4页Chinese Journal of Anesthesiology

基　　金：河南省教育厅科学技术研究重点项目（12A320039）

摘　　要：【摘要】目的评价CYP3A4＊1G基因多态性对硬膜外注射左旋布比卡因药代动力学的影响。方法择期硬膜外麻醉行下肢手术患者111例，ASA分级I或Ⅱ级，年龄30～60岁，体重56～79kg，麻醉前采集中心静脉血标本，采用聚合酶链反应一限制性片段长度多态性分析进行CYP3A4＊1G基因多态性检测，根据基因型将患者分为野生型纯合子组（w／w组）：基因型为CYP3A4＊1／＊1；突变型杂合子组（m／w组）：基因型为CYP3A4＊1／＊1G；突变型纯合子组（m／m组）：基因型为CYP3A4＊1G／＊1G。经L1,2行硬膜外穿刺，注射0．75％左旋布比卡因1．8mg／kg。随机选择34例患者，分别于注入左旋布比卡因后即刻、10、20、30、45、60、90、120、180、240、360、480、840和1440min时，采集中心静脉血样，采用高效液相色谱法测定血浆左旋布比卡因浓度，并计算其药代动力学参数。结果w／w组42例，m／w组59例，m／m组10例。111例下肢手术患者中CYP3A4＊1G等位基因频率为35．6％。3组患者不同时点血浆左旋布比卡因浓度、消除半衰期、清除率、分布容积、消除速率常数、峰值血药浓度、达峰时间和血药浓度一时间曲线下面积比较差异无统计学意义（P〉0．05）。结论CYP3A4＊1G基因多态性不是硬膜外注射左旋布比卡因药代动力学个体差异的遗传因素。Objective To evaluate the effect of CYP3A4＊1G genetic polymorphism on the pharma- cokinetics of levobupivacaine after epidural administration. Methods One hundred and eleven American Society of Anesthesiologists physical status I or I patients, aged 30-60 yr, weighing 56-79 kg, sched- uled for elective lower extremity surgery under epidural anesthesia, were enrolled in the study. Blood sam- ples were collected from the central vein before anesthesia for detection of CYP3Ad＊1G genotypes by poly- merase chain reaction-restriction fragment length polymorphism. The patients were divided into 3 groups ac- cording to the CYP3A4＊1G genotypes： wild hemozygote （CYP3A4＊1/＊1） group （w/w group）, mutation heterozygote （CYP3A4＊1/＊1G） group （m/w group） and mutation hemozygote （CYP3A4＊1G/＊1G） group （m/m group）. An epidural catheter was placed at the L~,： interspace, and 0. 75% levobupivacaine 1.8 mg/kg was injected. Thirty-four patients were randomly selected, and blood samples from the central vein were collected at0, 10, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 840 and 1 440 min after administration for determination of plasma concentrations of levobupivacaine by high-performance liquid chromatography. The pharmacokinetic parameters were calculated. Results There were 42 cases in group w/w, 59 cases in group m/w, and l0 cases in group m/m. The frequency of CYP3A4＊1G variant allele was 35.6% in the 111 patients underwent lower extremity surgery. There were no significant differences between the three groups in the plasma eoncentrations of levolmpivacaine at different time poinls, elimination half- life, clearance, distribution volume, elimination rate constant, peak plasma concentration, time to peak plasma concentration or area under the concentratiun-time curve （P〉O. 05）. Conclusion CYP3A4＊1G ge- netle polymorphism is not one of the genetic factors contributing to the individual variation in the pharmaco- kinetics of levobupivacaine alter epidural administration.

关 键 词：布比卡因 麻醉 硬膜外 细胞色素P-450 CYP3A 多态性 单核苷酸 药代动力学 

分 类 号：R969.1[医药卫生—药理学]