CYP2C19基因多态性与质子泵抑制剂对消化性溃疡患者抑酸效应的关系  

Relationship between the acid-suppression efficacy of proton pump inhibitors and the CYP2C19 genetic polymorphism in patients with peptic ulcer

作　　者：牛春燕[1] 罗金燕[2] 木尼拉[3] 王学勤[2] 

机构地区：[1]西安医学院附属医院消化内科,陕西省西安市710077 [2]西安交通大学第二医院消化内科,陕西省西安市710077 [3]新疆医科大学第一附属医院干部病房综合内科,新疆维吾尔自治区乌鲁木齐市830054

出　　处：《世界华人消化杂志》2007年第19期2151-2155,共5页World Chinese Journal of Digestology

摘　　要：目的:研究奥美拉唑(OME)、雷贝拉唑(RAB)及埃索美拉唑(ESO)对消化性溃疡患者的抑酸效应及与CYP2C19基因多态性的关系.方法:采用随机、开放和对照研究,将消化性溃疡患者59例随机分为3组,分别给予OME肠溶片(n=19)、RAB肠溶片(n=20)或ESO肠溶片(n=20)各20mg单剂量口服,动态监测24h胃内pH,观察3种药物对患者的24h和夜间抑酸效应及夜间酸突破(NAB)的影响.用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定所有患者的CYP2C19基因型并分为强代谢型(EMs)和弱代谢型(PMs).结果:OME组、RAB组及ESO组EM和PM的比例分别为16/3,17/3及17/3.OME24h抑酸与夜间抑酸效应(胃内pH>4的总时间和时间百分比)在PMs和EMs中的差异有显著性[24h抑酸:(胃内pH>4的总时间:10.65±2.3hvs7.22±2.1h,P<0.05;时间百分比:48.9±15.5vs32.5±12.6,P<0.05);夜间抑酸:(胃内pH>4的总时间:3.67±1.2hvs2.25±1.2h,P<0.05;时间百分比:38.3±20.6vs20.8±18.9,P<0.05)].而RAB及ESO组24h抑酸和夜间抑酸效应在PMs和EMs中的差异无显著性.RAB及ESO组NAB持续时间较OME组短(3.08±2.12h,2.98±2.73hvs4.50±2.86h,均P<0.05),NAB的pH高于OME组(2.15±0.70,2.45±0.65vs1.15±0.31,均P<0.001).RAB与ESO组间差异无显著性.结论:奥美拉唑的抑酸效应受患者CYP2C19基因多态性影响;雷贝拉唑和埃索美拉唑的抑酸效应则受CYP2C19基因多态性影响极小,3种PPIs的日间抑酸效应强于夜间,雷贝拉唑和埃索美拉唑的抑酸效应优于奥美拉唑.AIM： To investigate the acid-suppression efficacy of proton pump inhibitors （PPIs） in relation to the CYP2C19 genetic polymorphism in patients with peptic ulcer. METHODS： In an open, randomized controlled trial, 59 patients with active peptic ulcer were randomly assigned to receive one of three PPIs in a single dose （20 mg of each drug）： omeprazole （OME） （n = 19）, rabeprazole （RAB） （n = 20） and esomeprazole （ESO） （n = 20）. The level of 24 hours intragastric pH was dynamically moni-tored. The 24 hours and night acid-suppression effects of the three drugs were observed. The CYP2C19 genotype was detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） in all patients. RESULTS： The extensive metabolizers/poor metabolizers （EMs/PMs） ratio in the OME, RAB and ESO groups was 16/3, 17/3 and 17/3, respectively. The 24 hours and night acid-suppression effects [（total time and time percent （pH 〉 4）] in PMs were significantly higher than those in EMs in the OME group [24 hours acid suppres- sion： （total time： 10.65± 2.3 h vs 7.22 ± 2.1 h, P 〈 0.05; time percent： 48.9±15.5 vs 32.5 ± 12.6, P 〈 0.05）; and night acid suppression： （total time： 3.67 ± 1.2 h vs 2.25 ± 1.2 h, P 〈 0.05; time percent： 38.3 ± 20.6 vs 20.8 ± 18.9, P 〈 0.05）]. However, the above data showed that there was no significant difference between PMs and EMs in the RAB and ESO groups. The duration of nocturnal acid breakthrough in both the RAB and ESO groups was shorter than that in the OME group （3.08 ± 2.12 h and 2.98 ± 2.73 h vs 4.50± 2.86 h, both P 〈 0.05）, but the pH was higher （2.15 ± 0.70 and 2.45 ± 0.65 vs 1.15 ± 0.31, both P 〈 0.001）. There was no significant difference between the RAB and ESO groups for the above parameters. CONCLUSION The acid-suppression efficacy of OME is highly dependent on the CYP2C19 genetic polymorphism, while the CYP2C19 genetic polymorphism appears to have little influence on the

关 键 词：奥美拉唑 雷贝拉唑 埃索美拉唑 抑酸效 应 CYP2C19基因多态性 夜间酸突破 

分 类 号：R573.1[医药卫生—消化系统]