Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage

Background and Aim:  Proton pump inhibitors (PPI) are mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. We investigated whether the CYP2C19 genotype plays a role in the eradication rate of Helicobacter pylori ( H. pylori ) infection in patients receiving pantoprazole- or esomeprazole-based triple therapy.
Methods:  A total of 327 patients infected with H. pylori were treated with either pantoprazole or esomeprazole, plus amoxicillin and clarithromycin for 7 days. The presence of the CYP2C19 genotype was determined by pyrosequencing.
Results:  The overall H. pylori eradication rate was 85%; 82.6% for the PAC regimen, and 88.3% for the EAC regimen; the differences were not statistically significant. The overall eradication rate in the poor metabolizer groups (PM) was significantly higher than in the extensive metabolizer groups (EM) (97.4% vs 83.3%; P  = 0.016). The eradication rates in the EM and PM groups were 80.8% and 95.7% for the PAC regimen and 86.8% and 100% for the EAC regimen, respectively.
Conclusion:  The results of this study suggest that the CYP2C19 genotype status may play a role in the H. pylori eradication rate in patients receiving pantoprazole or esomeprazole-based triple therapy.     

埃索美拉唑三联疗法治疗幽门螺杆菌阳性十二指肠溃疡近期及远期疗效

目的评价埃索芙拉唑三联疗法治疗幽门螺杆菌（H．pylori）阳性十二指肠溃疡近期及远期H．pyloa根除率、溃疡愈合率和症状改善情况。方法50例幽门螺杆菌阳性的十二指肠溃疡患者随机分为两组：EAC组（埃索芙拉唑＋阿莫西林＋克拉霉素）和EFA组（埃索芙拉唑＋阿莫西林＋呋喃唑酮），疗程1周，比较治疗后第4周末和1年时H．pylori根除率和溃疡愈合率，同时比较用药第1，3，7，28d和1年时患者的症状改善情况。结果EAC组和EFA组问疗效比较差异无统计学意义；所有患者第4周末H．pylori根除率为90％（45／50），1年时H．pylori根除率为20％（10／50）；所有患者第4周末溃疡愈合率86％（43／50），1年时溃疡愈合率80％（40／50）。在治疗第7天时症状有效率最高，治疗前后症状有效率差异有统计学意义。结论埃索芙拉唑三联疗法治疗幽门螺杆菌阳性十二指肠溃疡近期H．pylori根除率低、溃疡愈合率和症状有效率高，远期溃疡愈合率和症状改善率也较高。但远期H．pylori根除率，这可能与H．pylori再感染有关。     

埃索美拉唑、克拉霉素、甲硝唑三联治疗儿童幽门螺杆菌感染的疗效

目的研究埃索美拉唑、克拉霉素、甲硝唑三联治疗儿童幽门螺杆菌(Hp)感染的疗效及安全性。方法经13C-尿素呼吸试验(13C-UBT)证实为Hp感染反复腹痛儿童98例,随机分为治疗组66例,予埃索美拉唑0.8mg/(kg.d),1次/d,克拉霉素15mg/(kg.d),2次/d,甲硝唑30mg/(kg.d),3次/d,三联治疗;对照组32例,予除奥美拉唑(0.8mg/kg,1次/d)外抗生素与治疗组相同,疗程1周。停药后4周门诊复诊并复查13C-UBT。结果二组儿童腹痛均有缓解,缓解率100%;Hp转阴60例,根除率90.9%。对照组转阴28例,根除率87.5%,二组幽门螺杆菌根除率无显著性差异(P>0.05)。结论埃索美拉唑、克拉霉素、甲硝唑三联治疗儿童Hp感染临床疗效好,Hp根除率高,未见明显不良反应,安全性好。     

阿莫西林克拉维酸钾联合方案与阿莫西林联合方案对消化性溃疡及根除HP疗效比较

目的比较阿莫西林克拉维酸钾联合治疗方案与阿莫西林联合治疗方案对消化性溃疡及根除幽门螺旋杆菌的疗效。方法选取我院门诊经胃镜及病理学检查确诊为消化性溃疡患者,经碳呼气试验确诊幽门螺旋杆菌感染385例,男224例,女161例,年龄17～74岁,平均年龄(34.8±14.4)岁,随机分为两组:治疗组193例,男115例,女78例;年龄18～74岁(平均35.2±14.7)岁。治疗方案为:埃索美拉唑20 mg,2次/d,克拉霉素500 mg,2次/d及阿莫西林克拉维酸钾分散片1 125 mg,2次/d,7 d后继续埃索美拉唑20 mg,2次/d,21 d。对照组192例,男109例,女83例;年龄17～65岁(平均34.5±13.6)岁。对照组为:埃索美拉唑20 mg,2次/d,克拉霉素500 mg,2次/d及阿莫西林1 000 mg,2次/d,7 d后继续埃索美拉唑20 mg,2次/d,21 d。结果治疗组和对照组的症状缓解率分别为97.9%和92.2%,溃疡愈合率分别为90.2%和85.4%,HP根除率分别为90.7%和82.3%。经比较均无统计学差异(P>0.05)。主要不良反应均是轻微可接受的。结论虽然阿莫西林克拉维酸钾联合治疗方案在症状缓解率、溃疡愈合率、HP根除率优于对照组,但是差异无统计学意义(P>0.05)。故是否应用阿莫西林克拉维酸钾代替阿莫西林根除HP尚有待进一步研究。     

HPLC法测定原料药中埃索美拉唑的含量

 目的 建立用于测定原料药中埃索美拉唑含量的HPLC法。方法 采用HPLC法测定,色谱柱:Waters XTerra- MS C8反相柱(150 mm×4.6 mm,3.5 μm),流动相:V(乙腈):V (20 mmol/L醋酸铵缓冲液,pH 7.6)=28:72,检测波长280 nm,柱温25 ℃,流速1 mL/min。 结果 埃索美拉唑浓度在0.01~0.07 mg/mL范围内与峰面积之间呈现良好的线性关系(r=0.9996),方法回收率为98.49%~101.72%,RSD为0.15%~0.58%。结论 本方法简便快速,能准确检测原料药中埃索美拉唑的含量,可作为原料药质量控制的分析方法。     

健康人口服单一剂量的雷贝拉唑与埃索美拉唑对胃酸抑制作用的比较

目的比较健康人口服雷贝拉唑10、20 mg和埃索美拉唑20、40mg对胃酸的抑制作用.方法本研究为多中心、单一剂量、多种用法、开放、随机自身对照性研究,10例HP感染阴性的健康志愿者,按随机顺序分别服用雷贝拉唑10和20 mg及埃索美拉唑20和40 mg,同步检测24h pH值,清洗期为14 d.结果服药前胃内pH基础值和服药后胃内pH的中位数之间均无显著性差异(P>0.05);各组单一剂量的雷贝拉唑和埃索美拉唑均能在3 h内出现抑酸作用,但雷贝拉唑10和20mg pH>4开始时间显著快于埃索美拉唑20和40 mg(P<0.05);胃内pH>4总时间的中位数,除雷贝拉唑20mg和埃索美拉唑40 mg显著长于埃索美拉唑20 mg外(P<0.05),其他剂量间相比较未见显著差别(P>0.05);白天pH>4的持续时间雷贝拉唑10和20mg与埃索美拉唑20和40 mg之间无显著差别,而夜间pH>4的持续时间雷贝拉唑20mg显著长于埃索美拉唑20 mg(P<0.01)和40 mg(P<0.05),并且雷贝拉唑10 mg夜间pH>4的时间也长于埃索美拉唑20mg(P<0.05);NAB的持续时间雷贝拉唑20 mg显著短于埃索美拉唑20 mg(P<0.01)和40 mg(P<0.05),并且雷贝拉唑10 mg和埃索美拉唑40 mg夜间酸突破的时间也显著较埃索美拉唑20 mg为短(P<0.05).结论HP阴性健康人口服单一剂量的雷贝拉唑10、20 mg和埃索美拉唑20、40mg都能有效地控制胃内酸度,不同的是小剂量的雷贝拉唑比埃索美拉唑发挥作用更快而且夜间抑酸作用更强;雷贝拉唑更适宜用于控制NAB.     

Development and validation of a DESI‐HRMS/MS method for the fast profiling of esomeprazole and its metabolites in rat plasma: a pharmacokinetic study

The advances in pharmaceutical development and drug discovery impose the availability of reliable high‐throughput screening methods for the rapid evaluation of drug metabolism and pharmacokinetic (PK) in biological samples. Here, a desorption electrospray mass spectrometry (DESI‐MS) method has been developed and validated for the PK profiling of esomeprazole and its metabolites (5‐hydroxyomeprazole and omeprazole sulfone) in rat plasma. Rats were treated with an esomeprazole solution (2.5 mg/mL) for endovenous administration and the analyte levels were profiled over 2 h after liquid‐liquid extraction from plasma. MS and tandem mass spectrometry (MS/MS) experiments were performed by using a DESI‐LTQ‐Orbitrap XL instrument and an on‐spot fixed time analysis on PMMA surfaces. Validation was performed for the esomeprazole. The DESI‐MS/MS method exhibited for the esomepazole excellent sensitivity (limit of detection (LOD)=60 ng/mL), linearity (0.2‐20 µg/mL concentration range; y=23848(±361)X, n=15; r²=0.987) and precision (RSD<9%) by using an internal standard method. The PK results were discussed in terms of Area Under the Curve, C_max and T_max. Data reliability was demonstrated by comparison with a liquid chromatography‐tandem mass spectrometry method (p>0.05). The data achieved demonstrated that the DESI‐MS method is suitable for sensitive and fast profiling of a drug and its metabolites at the therapeutic concentration levels. Copyright © 2015 John Wiley & Sons, Ltd.     

反相高效液相色谱法测定血浆中埃索美拉唑浓度

目的:建立反相高效液相色谱法测定人血浆中埃索美拉唑(esomeprazole,EMZ)浓度。方法:血浆样品用二氯甲烷萃取后经YMCC18(150mm×4·6mm,5μm)色谱柱(柱温:35℃),用流动相甲醇-0·02mol·L-1醋酸铵(NH3·H2O调pH7·6)=51:49,以流速1ml·min-1洗脱分离,用卡马西平为内标,检测波长306nm。结果:标准曲线线性范围3·9~2000·0ng·ml-1;萃取回收率70·6%~76·7%;加样回收率89·1%~104·6%;日内测定RSD为4·8%~6·6%,日间测定RSD为2·8%~5·6%。结论:本方法快速、灵敏、准确、简便,适用于EMZ血药浓度测定及药代动力学研究。