细胞色素P450 2C19基因多态性对雷贝拉唑抑酸效应的影响

背景:研究表明细胞色素P4502C19(CYP2C19)参与质子泵抑制剂(PPIs)的代谢,是奥美拉唑、兰索拉唑和泮托拉唑的主要代谢途径。而雷贝拉唑主要经非酶途径代谢,只有一小部分经CYP2C19途径代谢。目的:研究CYP2C19基因多态性(表型多态性)对雷贝拉唑抑酸效应的影响,阐明用雷贝拉唑治疗酸相关疾病时区分CYP2C19基因型的必要性。方法:36名健康志愿者参与本研究。采用聚合酶链反应鄄限制性片段长度多态性(PCR鄄RFLP)方法确定CYP2C19基因型,据此将志愿者分为CYP2C19强代谢型组(n=24)和弱代谢型组(n=12)。给予两组志愿者雷贝拉唑20mg单剂量口服,动态监测24h胃内pH。结果:CYP2C19强代谢型组与弱代谢型组胃内pH>3的抑酸起效时间无显著差异(177.50min±20.09min对146.65min±12.30min,P>0.05)。强代谢型组24h胃内pH>4的总时间(769.67min±107.50min)和时间百分比(61.6%±9.4%)与弱代谢型组(912.00min±87.67min和65.7%±6.4%)相比差异无显著性(P>0.05);两组24h胃内pH的中位数和均值差异亦无显著性(4.92±1.53对5.30±0.33和4.97±0.72对4.97±0.21,P>0.05)。结论:雷贝拉唑在不同CYP2C19基因型志愿者中的抑酸效应相同,提示雷贝拉唑治疗酸相关疾病的疗效不依赖于CYP2C19基因多态性。     

埃索美拉唑对健康志愿者抑制胃泌酸的药效学研究

目的　比较埃索美拉唑与雷贝拉唑对健康志愿者抑制胃泌酸的效果及安全性。方法　 36名健康志愿者随机分为两组 ,分别口服埃索美拉唑 4 0mg或雷贝拉唑 10mg ,每日 1次 ,连续 5d ,经过14d的洗脱期后 ,交叉口服雷贝拉唑 10mg或埃索美拉唑 4 0mg ,每日 1次 ,连续 5d。分别于服药首日及第 5天连续测定 2 4h胃内 pH ,并以PCR方法鉴定细胞色素 (CYP) 2C19基因型。 结果　埃索美拉唑组服药后首日最初 4、2 4h和第 5天 2 4h胃内pH >4 .0的时间百分比分别为 5 8.9%、73.7%和 84 .2 % ,显著高于雷贝拉唑组 (32 .1%、5 4 .8%和 76 .2 % ,P <0 .0 0 1) ;胃内 pH中位值分别为 4 .2 9、5 .6 0和 6 .38,亦显著高于雷贝拉唑组 (2 .88、4 .2 6和 5 .77,P≤ 0 .0 0 1)。服药后首日及第 5天pH >4 .0超过 16h的志愿者埃索美拉唑组百分率分别为 6 3.9%和 88.9% ,亦显著高于雷贝拉唑 (33.3%和 6 1.1% ,P <0 .0 5 )。36名志愿者中 2 8名CYP 2C19基因型为强代谢型 ,8名为弱代谢型。两药对强代谢型或弱代谢型者胃泌酸的抑制差异无显著性 (P >0 .0 5 )。服药期间两组均未发生明显不良反应。结论　埃索美拉唑和雷贝拉唑均具有较强的抑制胃酸分泌效应 ,但在抑酸速度、抑酸强度和维持时间方面 ,4 0mg埃索美拉唑优于 10mg雷贝拉唑。两药     

CYP2C19基因多态性对雷贝拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 分析CYP2C19基因多态性在含雷贝拉唑的不同三联方案中对幽门螺杆菌(Hp)根除率的影响。方法 连续收集128例Hp培养阳性的病人随机进入雷贝拉唑联合克拉霉素与羟氨苄青霉素方案(RAC)或雷贝拉唑联合羟氨苄青霉素与甲硝唑方案(RAM)进行1周根除治疗。治疗前CYP2C19基因多态性通过PCR-限制性片段长度多态性进行鉴定,治疗结束至少4周后Hp的状态用”C-呼气试验进行检测。结果 在128例病人中纯合子强代谢型(hom-Ems)、杂合子强代谢型(het-Ems)、弱代谢型(PMs)分别为30．5％、50．0％、19．5％。在无克拉霉素、甲硝唑耐药菌株的情况下,RAC方案与RAM方案的Hp根除率分别为98．1％与91．3％(按治疗方案分析)。但是,甲硝唑的耐药率高达66．8％,降低了RAM方案的Hp根除率。logistic回归分析显示不同的CYP2C19基因型对Hp的根除率没有显著的影响。结论 以雷贝拉唑为基础的三联疗法根除Hp无明显个体差异,RAC的治疗方案值得推荐。     

细胞色素P450 2C19基因多态性对以质子泵抑制剂为基础的三联疗法根除幽门螺杆菌疗效的影响

目的 研究以质子泵抑制剂(PPI)、左氧氟沙星、羟氨苄青霉素作为一线疗法对幽门螺杆菌(Hp)根除的影响,以及Hp根除率与CYP2C19基因多态性的相关性.方法 205例Hp阳性的患者被分为4组:埃索美拉唑20 mg 2次/d(E_(20)组),埃索美拉唑40 mg 2次/d(E_(40)组),雷贝拉唑10 mg 2次/d(R组),兰索拉唑30 mg 2次/d(L组),4组均加左氧氟沙星500 mg 1次/d和羟氨苄青霉素1000 mg 2次/d,疗程1周.其中有161例患者进行了CYP2C19基因型的检测,对Hp根除率分别按意愿治疗(intention-to-treat,ITT)分析和按方案(per protocol,PP)分析进行评估.结果 Hp总根除率为83.4%(PP)和79.0%(ITT).各组的根除率为:E_(20)组86.7%,E_(40)组88.5%,R组73.5%,L组78.1%.其中完成基因型检测的161例患者中,各基因型的根除率分别为:纯合子弱代谢型(PM)90%,杂合子强代谢型(HetEM)81.5%,纯合子强代谢型(HomEM)82.1%.CYP2C19各基因型间Hp根除率、各治疗方案间的根除率及各方案内各基因型间的根除率差异均无统计学意义(P>0.05).结论 以PPI为基础包含左氧氟沙星的三联疗法是目前根除Hp的有效方案,且该方案对Hp的根除率不受CYP2C19基因多态性的影响.     

HPLC法对雷贝拉唑钠肠溶片血药浓度与CYP2C19基因多态性调控机制

目的对雷贝拉唑钠肠溶片与CYP2C19基因多态性的相关性进行研究.方法随机选取2012-06/2015-08建德市中医院征集的300名志愿者,让这些志愿者各自服用20 m g雷贝拉唑钠肠溶片,并在12 h后收集血样,用高效液相色谱法(high performance liquid chromatography,HPLC)测定血药浓度;在此之后,分别对所有受试者的等位基因CYP2C19*2、CYP2C19*3、CYP2C19*17突变情况进行检测,并依据检测的基因型将志愿者分为不同的表现型组,再根据基因型和血药浓度研究不同表现型组中药动学参数存在的差异.结果将3 0 0名志愿者的血药浓度数据进行统计分析,结果显示其基因型表现情况为:CYP2C19*1/*1(homEMs,60例)、CYP2C19*1/*2(het EMs,200例)、CYP2C19*2/*2(PMs,40例),无CYP2C19*17这一基因型.对药动学参数进行对比分析,结果发现3组中的T_(max)并无明显变化(P0.0 5);任意两组进行对比,t1/2均有显著差异(P0.05);在hom EMs、het EMs和homEMs、PMs中,肠溶片参数AUC_(0-1)、AUC_(0-∞)均存在较大差异(P0.05);Cmax在homEMs、het EMs两组中差异显著(P0.05).结论HPLC法在研究雷贝拉唑钠肠溶片人体药动学方面具有简便、准确的优点;CYP2C19基因多态性对雷贝拉唑钠肠溶片的t1/2、AUC、C_(max)均有影响.     

奥美拉唑治疗反流性食管炎的疗效与CYP2C10基因多态性的关系

目的 探讨短期应用奥美拉唑治疗反流性食管炎的疗效及其与CYP2C19基因多态性的关系.方法 应用奥美拉唑20 mg每日晨起空腹口服1次,持续4周,治疗56例经胃镜证实的反流性食管炎患者.记录治疗前和用药2周后、4周后时症状的变化,并于治疗结束时复查胃镜.受试者CYP2C19的基因型检测采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析方法 .结果 纯合子强代谢组、杂合子强代谢组和弱代谢组胃镜下治愈率分别为47.37%、69.23%和88.89%,纯合子强代谢组的治愈率显著低于弱代谢组(P＜0.05).结论 CYP2C19基因多态性与奥美拉唑治疗反流性食管炎的疗效密切相关.CYP2C19基因分型检测是临床治疗酸相关性疾病中的一个重要的工具.     

奥美拉唑治疗反流性食管炎的疗效与CYP2C19基因多态性的关系

目的探讨短期应用奥美拉唑治疗反流性食管炎的疗效及其与CYP2C19基因多态性的关系。方法应用奥美拉唑20mg每日晨起空腹口服1次,持续4周,治疗56例经胃镜证实的反流性食管炎患者。记录治疗前和用药2周后、4周后时症状的变化,并于治疗结束时复查胃镜。受试者CYP2C19的基因型检测采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）分析方法。结果纯合子强代谢组、杂合子强代谢组和弱代谢组胃镜下治愈率分别为47.37％、69.23％和88.89％,纯合子强代谢组的治愈率显著低于弱代谢组（P〈0.05）。结论CYP2C19基因多态性与奥美拉唑治疗反流性食管炎的疗效密切相关。CYP2C19基因分型检测是临床治疗酸相关性疾病中的一个重要的工具。     

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

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20 mg单剂量口服, 动态监测24 h胃内pH, 观察3种药物对患者的24 h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. OME 24 h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[24 h抑酸: (胃内pH>4的总时间: 10.65±2.3 h vs 7.22±2.1 h, P<0.05;时间百分比: 48.9±15.5 vs 32.5±12.6, P<0.05);夜间抑酸: (胃内pH>4的总时间: 3.67±1.2 h vs 2.25±1.2 h, P<0.05;时间百分比: 38.3±20.6 vs 20.8±18.9, P<0.05)]. 而RAB及ESO组24 h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±2.12 h, 2.98±2.73 h vs 4.50±2.86 h, 均P<0.05), NAB的pH高于OME组(2.15±0.70, 2.45±0.65 vs 1.15±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.     

新疆喀什地区汉族与维吾尔族心脑血管疾病患者 CYP2 C19基因多态性分析

目的：分析新疆喀什地区汉族、维吾尔族心脑血管疾病患者CYP2C19基因多态性。方法新疆喀什地区的1020例心脑血管疾病患者,其中汉族220例、维吾尔族800例,采用基因芯片技术检测CYP2 C19基因多态性,并对汉族和维吾尔族患者CYP2C19等位基因频率和代谢表型频率进行比较。结果汉族患者CYP2C19＊1频率为0．6454,维吾尔族患者为0．7869,两者比较P＜0．05;汉族患者＊2频率为0．3273,维吾尔族患者为0．1837,两者比较P＜0．05。汉族、维吾尔族患者代谢表型为强代谢型纯合子频率分别为42．72％、62．13％,两者比较P＜0．01;强代谢型杂合子频率分别为43．64％、33．13％,两者比较P＜0．01;弱代谢型频率分别为13．64％、4．76％,两者比较P＜0．01。结论在新疆喀什地区汉族和维吾尔族心脑血管疾病患者中,CYP2C19的基因型分布具有差异。维吾尔族患者的强代谢基因型高于汉族患者,汉族患者的慢代谢基因型高于维吾尔族患者。     

老年糖尿病患者CYP2C19基因多态性与氯吡格雷抵抗的相关性

目的探讨老年糖尿病患者CYP2C19基因多态性与氯吡格雷抵抗发生的相关性。方法72例初步诊断为急性冠脉综合征、糖尿病的老年（〉65岁）患者纳入本研究,给予阿司匹林及氯吡格雷口服,并经血栓弹力图检测氯吡格雷抑制率,氯吡格雷抑制率〈50％定义为氯吡格雷抵抗。采用基因芯片检测技术检测CYP2C19基因多态性,进一步探讨CYP2C19基因多态性与氯吡格雷抵抗发生的相关性。结果72例患者中,纯合子强代谢型（CYP2C191／1）19例（26．4％）,杂合子强代谢型（CYP2C191／2,CYP2C19六1／3）36例（50％）,弱代谢型（CYP2C19-k2／2,CYP2C19六2／六3）17例（23．6％）,三种代谢组中出现氯吡格雷抵抗的概率分别为36．8％、52．8％和82．4％,差别有统计学意义。结论老年糖尿病患者CYP2C19基因多态性与氯吡格雷抵抗的发生具有相关性。     

Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans

AIM: To observe the pharmacokinetics and pharmaco-dynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.     

Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation

Background and Aim: The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration‐time curve (AUC) and the pH elevation were studied in GERD patients. Methods: Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori‐negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication. Results: The AUC in the PM group (957 ng·h/mL) was significantly higher than those of homEM (375 ng·h/mL) and hetEM (542 ng·h/mL) groups. Median 24‐h pH curves, median 24‐h pH values and 24‐h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes. Conclusion: The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype‐independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8‐week administration of rabeprazole.     

质子泵抑制剂抑酸效果与肝药酶基因型的关系

目的　比较质子泵抑制剂雷贝拉唑 (Rab)与奥美拉唑 (Ome)对十二指肠球部溃疡 (DU)患者抑酸效果和夜间酸突破 (NAB)的影响及其与肝药酶S 美芬妥英羟化酶 (CYP2C19)基因型的关系。方法　 30例DU病人随机分 2组 ,每组 15例 ,分别接受Rab (10mg ,每日 2次口服 )或Ome (2 0mg ,每日 2次口服 )治疗 ,用药 2 4h起连续 2 4h监测胃内pH值 ,并采用PCR结合限制性内切酶技术进行CYP2C19基因型分析。结果　基因型为弱代谢 (PM)、强代谢中的突变型杂合子 (hetEM)及野生型纯合子者 (homEM)的平均胃内pH值在Rab组中分别为为 6 3± 0 1、6 1± 0 2、6 0± 0 1,两两间比较差异无显著性 (P >0 0 5 ) ;Ome组中分别为 6 3± 0 1、5 9± 0 2、5 6± 0 3,两两间比较差异有显著性 (P <0 0 5 )。Rab组平均胃内pH值和平均中位pH值分别为 6 1± 0 2和 6 1± 0 3,高于Ome组的 5 8± 0 4和 5 7± 0 4 (P <0 0 5 ) ,原因在于homEM型平均胃内pH值 (6 0± 0 1)较Ome组 (5 6± 0 3)显著升高(P <0 0 5 )。Rab和Ome组各有 3例NAB(占 2 0 % ) ,且均在EM者 ,NAB持续时间在Rab组较Ome组短 ,分别为 (2 6± 0 2 )h和 (3 4± 0 6 )h。结论　Rab的抑酸作用较Ome少受肝药酶CYP2C19基因型的影响。Rab抑酸水平较Ome强     

Effect of esomeprazole and rabeprazole on intragastric pH in healthy Chinese: an open, randomized crossover trial

BACKGROUND AND AIM: Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese. METHODS: Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM). RESULTS: The percentage of time with intragastric pH >4 was significantly higher (P < 0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (P 4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P < 0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH >4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated. CONCLUSIONS: Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.     

The clinical role of cytochrome p450 genotypes in Helicobacter pylori management

OBJECTIVE: The aim of this pharmacogenomics study was to investigate the influence of different cytochrome P450 (CYP) genotypes in Helicobacter pylori eradication therapy. METHOD: The study involved 143 consecutive Italian Caucasian patients with H. pylori infection diagnosed and treated with 1-wk triple therapy according to European Helicobacter Pylori Study Group guidelines. Using human genomic DNA, CYP2C19 (*2 and *3) and CYP3A4 alleles (*1B, *2, and *3) were evaluated by polymerase chain reaction-restriction fragment length polymorphism assays and confirmed by sequencing the amplicons. RESULT: According to the endoscopy-based gold standard, 93 patients achieved H. pylori eradication. Regarding CYP2C19 genotype, the 50 patients who remained infected were all homozygous or heterozygous extensive metabolizers (homEM or hetEM). Carriers of homEM fared significantly less well than those of hetEM; homEM genotype was also predictive of failure at univariate/multivariate analysis. Carriers of CYP3A4 polymorphisms achieved favorable eradication rates similar to patients bearing CYP2C19. All four patients with single CYP3A4*2 polymorphism achieved eradication, and only 29% (5/17) of all CYP3A4*1B carriers did not achieve eradication. All nine patients carrying CYP3A4 polymorphisms in the CYP2C19 hetEM subgroup were cured, suggesting the possibility of a positive synergism between CYP3A4 and CYP2C19. CONCLUSIONS: This first pharmacogenomics study on the influence of different CYP genotypes on H. pylori therapy suggests that, as in Asian populations, CYP2C19 genotype patterns are probably also relevant in Caucasians receiving H. pylori eradication regimens that include omeprazole. The possibility of a favorable drug interaction mediated by CYP2C19 and CYP3A4 requires investigation.     

Comparison of the effect on intragastric pH of a single dose of omeprazole or rabeprazole: Which is suitable for on‐demand therapy?

BACKGROUND AND AIMS: An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole. METHODS: Fourteen Helicobacter pylori-negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH > 3 and> 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH > 2,> 3,> 3.5 and> 4 for longer during the 6 h study period than did omeprazole. CONCLUSIONS: In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole.     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

雷贝拉唑对重症急性胰腺炎患者上消化道出血的预防作用

背景:重症急性胰腺炎(SAP)是一种临床常见的危重疾病,急性胃黏膜病变引起的上消化道出血是SAP较为常见的并发症。目的:观察雷贝拉唑对SAP患者上消化道出血的预防作用。方法:30例SAP患者随机分为两组,分别予雷贝拉唑20mg每日1次口服(n=20)和法莫替丁40mg每日2次静脉滴注(n=10),疗程1周。于用药前24h至用药后72h连续监测上消化道出血的发生情况和胃内pH的变化。结果:雷贝拉唑组患者无呕血和黑粪出现,法莫替丁组有1例患者出现黑粪,发生率为10%。用药后,两组患者的胃内pH和pH>3、pH>4、pH>5的时间百分比均显著升高,雷贝拉唑组升高较法莫替丁组显著(P<0.05)。两组患者均未发生明显不良反应。结论:雷贝拉唑和法莫替丁均能升高SAP患者的胃内pH,对上消化道出血有预防作用,且无明显不良反应。雷贝拉唑维持胃内较高pH的时间较法莫替丁更长。