CYP2C19基因多态性对侵袭性真菌感染重症患者伏立康唑血药浓度的影响

目的:研究CYP2C19基因多态性与侵袭性真菌感染重症患者伏立康唑标准化血药浓度的关系,为临床合理用药提供参考。方法:运用PCR-RFLP方法对患者CYP2C19 2(681G→A)和CYP2C19 3(636 G→A)位点进行基因型分析;使用HPLC法检测49名侵袭性真菌感染患者的伏立康唑血药浓度;并对伏立康唑血药浓度检测结果、药物疗效和不良反应与基因分型结果进行统计学分析。结果:49名患者中,同时分析CYP2C19两个位点,共有5种双位点基因型组合,包括强代谢型(extensive metabolizer,EM)的681GG-636GG、中等代谢型(intermediate metabolizer,IM)的681GA-636GG和681GG-636GA以及慢代谢型(poor metabolizer,PM)的681AA-636GG和681GA-636GA,其分布频率分别为14.29%,53.06%,8.16%,14.29%和10.2%。EM组、IM组和PM组的标准化血药浓度存在显著性差异(P<0.05),且PM组显著高于IM组,IM组显著高于EM组(P<0.05)。此外,基因多态性对各组间的药物疗效(P<0.05)和不良反应(P<0.05)均具有显著性影响。结论:CYP2C19基因多态性对伏立康唑血药浓度、疗效和不良反应产生显著影响,表明药物遗传学研究对伏立康唑临床合理用药具有重要的指导意义。     

中国人群中CYP2C19基因多态性对质子泵抑制药治疗消化性溃疡疗效影响的Meta分析

摘 要 目的：采用Meta分析方法评价中国人群中药物代谢酶CYP2C19基因多态性与质子泵抑制药对消化性溃疡愈合率的关系,以期为临床用药与基因检测提供循证依据。方法: 检索SinoMed、中国知网、维普期刊数据库、万方数据库、PubMed、Embase中有关CYP2C19基因多态性与质子泵抑制药治疗消化性溃疡的临床研究文献。根据纳入和排除标准筛选文献、评价和提取数据后,采用RevMan 5.3与Stata 13.0软件进行Meta分析。结果: 共纳入8篇文献,包含1 197例对象。Meta分析结果显示：不考虑质子泵抑制药类型,CYP2C19强代谢型（EM）的消化性溃疡愈合率低于与中间代谢型（IM）（OR=0.63,95%CI：0.46~0.86,P<0.05）,EM型的消化性溃疡愈合率低于与弱代谢型（PM）（OR=0.45,95%CI：0.29~0.69,P<0.05）,但IM型与PM型消化性溃疡愈合率的差异无统计学意义（OR=0.68,95%CI：0.44~1.04,P>0.05）。亚组分析仅发现同样结果存在于奥美拉唑中,EM型消化性溃疡愈合率低于IM型低（OR=0.59,95%CI：0.36~0.97,P<0.05）,EM型消化性溃疡愈合率亦低于PM型（OR=0.29,95%CI：0.13~0.62,P<0.05）,但IM型与PM型的差异无统计学意义（P>0.05）。其他质子泵抑制药如雷贝拉唑、埃索美拉唑、艾普拉唑等未发现上述差异。结论: 中国人群中CYP2C19基因多态性影响奥美拉唑的消化性溃疡愈合率疗效,但不影响埃索美拉唑、雷贝拉唑、艾普拉唑等其他质子泵抑制药的疗效。因此,在应用奥美拉唑治疗消化性溃疡时,有必要对患者的CYP2C19进行基因检测,以指导个体化给药方案的制订。     

多药耐药基因MDR1 C3435T基因多态性对质子泵抑制剂三联方案根除幽门螺杆菌疗效影响的Meta分析

目的:系统评价多药耐药基因MDR1 C3435T基因多态性与质子泵抑制剂三联方案根除幽门螺杆菌疗效的关系,为临床提供循证参考。方法:计算机检索Pub Med、EMBase、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CJFD)、万方数据库、中文科技期刊数据库(VIP),收集MDR1 C3435T基因多态性对质子泵抑制剂三联方案根除幽门螺杆菌感染疗效的临床研究,提取资料并按照STREGA声明评价质量,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入7项研究,合计1 019例患者。按照患者MDR1 C3435T基因型检测结果分为野生纯合子基因(CC)型组,突变杂合子基因(CT)型组与突变纯合子基因(TT)型组。Meta分析结果显示,MDR1 C3435T基因多态性中CC组、CT组与TT组患者幽门螺杆菌根除率比较,差异均无统计学意义[CC vs.CT:OR=0.99,95%CI(0.69,1.42),P=0.95;CC vs.TT:OR=1.44,95%CI(0.66,3.15),P=0.36;CT vs.TT:OR=1.54,95%CI(0.86,2.73),P=0.14];亚组分析发现,亚洲人群中CT组患者幽门螺杆菌根除率显著高于TT组,差异有统计学意义[OR=2.35,95%CI(1.53,3.62),P<0.001]。结论:MDR1 C3435T基因多态性基本不影响质子泵抑制剂三联方案根除幽门螺杆菌的疗效,但亚洲人群进行治疗时,参考基因检测结果有一定意义。     

雷贝拉唑联合四联疗法治疗不同CYP2C19基因代谢型幽门螺旋杆菌阳性慢性胃炎的疗效观察

目的探讨雷贝拉唑钠肠溶片联合四联疗法治疗不同细胞色素氧化酶P450 2C19(CYP2C19)基因代谢型幽门螺旋杆菌阳性慢性胃炎的临床疗效。方法选取2015年2月—2018年10月在西安市第一医院消化科住院的240例幽门螺旋杆菌阳性慢性胃炎患者作为研究对象,经基因检测确定了CYP2C19基因型,其中快代谢型(EM)、中等代谢型(IM)、慢代谢型(PM)各80例。每种代谢型患者再随机分为对照组和治疗组,每组各40例。对照组患者均行四联疗法,静脉泵入注射用泮托拉唑钠,40 mg溶于生理盐水50 mL,2次/d;静脉泵入注射用阿莫西林钠克拉维酸钾,1.2 g溶于生理盐水50 mL,2次/d;口服胶体酒石酸铋胶囊220mg,2次/d;口服克拉霉素片,500mg/次,2次/d。治疗组在对照组治疗的基础上口服雷贝拉唑钠肠溶片,1片/次,2次/d。两组患者均连续治疗14 d。完全停药1月后行呼气试验检测。观察患者的幽门螺旋杆菌根除率,比较不良反应发生情况。结果 EM型治疗组与对照组根除率比较,差异具有统计学意义(P0.05);IM型、PM型治疗组与对照组根除率比较,差异无统计学意义。3个治疗组中,PM型根除率(95.0%)最高,IM型根除率(77.5%)次之,EM型根除率(57.5%)最低,组间根除率比较差异具有统计学意义(P0.05)。3个对照组中,PM型根除率(97.5%)最高,IM型根除率(92.5%)次之,EM型根除率(82.5%)最低,组间根除率比较差异无统计学意义。结论以泮托拉唑静点为基础的四联疗法受CYP2C19基因多态性的影响小。但对于快代谢型加用雷贝拉唑钠肠溶片可提高幽门螺旋杆菌根除率,效果较中等代谢型、慢代谢型明显。     

幽门螺杆菌根除疗效与CYP2C19基因多态性的相关性研究

目的：研究和分析幽门螺杆菌根除疗效与CYP2C19基因多态性的相关性。方法：收集慢性胃溃疡患者100例,随机分为观察组与对照组,各50例,两组患者均使用克拉霉素和阿莫西林进行治疗后,对照组患者使用埃索美拉唑进行治疗,观察组患者使用兰索拉唑进行治疗,将两组患者的CYP2C19基因型进行测定和对比,在治疗结束后对幽门螺杆菌的根除效果进行检测。结果：观察组患者和对照组患者的幽门螺杆菌根除率,以P＞0.05表示差异无统计学意义;通过CYP2C19基因分型,对照组患者中弱代谢型、中间代谢型和快代谢型的幽门螺杆菌根除率无显著差异（P＞0.05）;而观察组弱代谢型的根除率明显高于快代谢型（P<0.05）。结论：在幽门螺杆菌的根除治疗过程中,通过CYP2C19基因多态性的检测,能够提供有效的用药选择参考价值。     

CYP2C19基因多态性对雷贝拉唑与奥美拉唑四联治疗幽门螺杆菌阳性胃溃疡疗效的影响

目的:分析CYP2C19基因多态性对雷贝拉唑和奥美拉唑四联治疗幽门螺杆菌(Hp)阳性胃溃疡疗效的影响。方法:选取Hp阳性胃溃疡患者168例,随机分为2组。观察组接受雷贝拉唑四联疗法,对照组接受奥美拉唑四联疗法,治疗结束4周后比较2组患者胃肠道症状改善情况、临床疗效、Hp根除率及不良反应发生情况。同时利用DNA微阵列芯片法检测患者的CYP2C19基因型,观察基因型对两组药物疗效的影响。结果:观察组治愈率72.62%,总有效率89.28%,Hp根除率95.23%,对照组治愈率58.34%,总有效率72.62%,Hp根除率86.90%,两组差异显著(P<0.05或P<0.01)。观察组中,快代谢型(EM)治愈率61.12%,中间代谢型(IM)80.00%,弱代谢型(PM)84.62%,EM型与IM及PM型间差异极显著(P<0.01),IM型与PM型之间无显著性差异(P>0.05)。对照组中,EM型治愈率44.74%,IM型64.71%,PM型83.34%,3种代谢型间的治愈率差异极显著(P<0.01)。相同代谢型患者治愈率两组间比较,PM型无明显差异(P>0.05),但EM型与IM型观察组均明显高于对照组(P<0.05)。结论:雷贝拉唑四联疗法较奥美拉唑四联疗法治疗Hp阳性胃溃疡根除率更高,疗效更显著,安全性相当,且受CYP2C19基因型影响程度较小,疗效更稳定,值得临床推荐。     

根除幽门螺杆菌感染失败与细胞色素P450酶2C19基因变异的关系

目的 探讨根除幽门螺杆菌感染失败与细胞色素P450酶2C19(CYP2C19)基因变异的关系.方法 选取60例Hp根除失败患者,对CYP2C19进行基因检测,其中基因强代谢者(EM)49例为观察组,弱代谢者(PM)11例为对照组,均予以使用埃索美拉唑的三联疗法治疗,治疗结束后复查14C转阴率.结果 观察组49例患者Hp根除率为79.6％,对照组为Hp根除率为100.0％,对照组优于观察组(X2=9.475,P＜0.05).结论 Hp根除失败患者中CYP2C19强代谢型(49/60)为多,再次予以埃索美拉唑治疗可提高强代谢型的疗效,但对弱代谢型基因疗效为佳.     

白介素1β基因多态性对质子泵抑制剂三联方案根除幽门螺杆菌疗效影响的Meta分析

目的 系统评价白介素1β（interleukin-1β,IL-1β）基因多态性与质子泵抑制剂三联方案根除幽门螺杆菌疗效的关系。方法 检索PubMed、Embase、CBM、CNKI、Wanfang data、CQVIP等数据库,收集IL-1β基因多态性（C-511T、T-31C）与质子泵抑制剂三联方案根除幽门螺杆菌感染的临床文献。根据纳入和排除标准筛选文献、评价和提取数据后,采用RevMan 5.3软件进行meta分析。结果 共纳入4篇文献,包含1 123例对象。Meta分析结果显示,IL-1β C-511T基因多态性中仅CC与TT基因型间质子泵抑制剂三联疗法的幽门螺杆菌根除率存在统计学差异（78.5%vs 92.1%,P<0.05）;CT与CC或TT基因型间幽门螺杆菌根除率无统计学差异（87.7%vs 78.5%,87.7%vs 92.1%）。IL-1β T-31C基因多态性中TT、TC与CC基因型间质子泵抑制剂三联疗法的幽门螺杆菌根除率无统计学差异（87.9%,84.6%,96.2%）。结论 IL-1β C-511T基因多态性可能影响质子泵抑制剂三联方案根除幽门螺杆菌的疗效。     

CYP2C19基因多态性对奥美拉唑治疗儿童幽门螺旋杆菌疗效的影响

目的：探索儿童CYP2C19的基因分布,以及基因多态性对奥美拉唑治疗儿童幽门螺旋杆菌疗效的影响。方法：收集本院消化科住院治疗的111例幽门螺旋杆菌阳性患儿血样,采用数字荧光杂交测定CYP2C19的基因型,根据结果分为4种代谢类型：超快代谢型（UM）、快代谢型（EM）、中间代谢性（IM）以及慢代谢型（PM）,统计不同基因型、代谢型分布频率。常规奥美拉唑剂量下[0.6~1 mg·（kg·d）^-1（最大量40 mg·d^-1）],比较不同代谢型患儿幽门螺旋杆菌根除率。快代谢组患儿,比较奥美拉唑常规剂量组和高剂量组[1.2~2 mg·（kg·d）^-1（最大量80 mg·d^-1）]的根除率。结果：CYP2C19*1、CYP2C19*2、CYP2C19*3和CYP2C19*17等位基因频率分别为67.12%,24.77%,6.76%和1.35%。UM型、EM型、IM型以及PM型代谢组分布频率分别为0.9%,50.45%,34.23%,14.41%。常规奥美拉唑剂量下,EM组根除率（53.57%）显著低于IM（78.95%）及PM组（87.5%）。快代谢组患儿,高剂量组根除率（82.14%）显著高于常规剂量组（53.57%）。结论：剂量相同的条件下,EM组的根除率更低,但增加剂量可以提高EM组的根除率,这可用于指导临床个体化用药。通过基因检测,可以选择更合适的药物剂量。     

亚洲炎症性肠病患者中NUDT15 R139C基因多态性与巯嘌呤类药物诱导的白细胞减少的Meta分析

目的：系统评价亚洲炎症性肠病患者中NUDT15 R139C基因多态性与巯嘌呤类药物诱导的白细胞减少的关系。方法：计算机检索PubMed、Embase、Web of Science、CNKI和万方等数据库中NUDT15 R139C基因多态性与巯嘌呤诱导的白细胞减少的相关研究,检索时间均为建库至2018年6月。由2位评价员独立筛选文献、提取资料并评价纳入研究的质量,采用Revman 5.3软件进行Meta分析。结果：共纳入8个研究,3 676例炎症性肠病患者,Meta分析结果表明：NUDT15 R139C纯合突变与杂合突变者发生白细胞减少的风险显著高于野生型患者,差异有显著性（[TT&CC：OR=73.24,95% CI（32.81,163.47）,P<0.000 01;TC&CC：OR=5.99,95% CI（4.97,7.22）,P<0.000 01;TT+TC&CC：OR=7.33 95% CI（6.12,8.78）,P<0.000 01]）;此外还发现,NUDT15 R139C纯合突变与杂合突变者发生早期白细胞减少的风险[TT&CC：OR=56.90,95% CI（25.40,127.49）,P<0.000 01;TC&CC：OR=2.20,95% CI（1.42,3.41）,P=0.000 2;TT+TC&CC：OR=6.19,95% CI（2.76,13.85）,P=0.002]、严重白细胞减少的风险[TT&CC：OR=34.32,95% CI（16.74,70.37）,P<0.000 01;TC&CC：OR=2.50,95% CI（1.54,4.05）,P=0.000 2;TT+TC&CC：OR=4.87 95% CI（3.13,7.59）,P<0.000 01]均较野生型患者高,差异有显著性。结论：在炎症性肠病患者中,NUDT15 R139C基因突变患者使用巯嘌呤药物发生白细胞减少、早期白细胞减少、严重白细胞减少的风险显著高于野生型,临床上NUDT 15R139C基因型的测定可对巯嘌呤类药物个体化治疗提供有力的帮助。     

Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics for 1 week-a meta-analysis of efficacy

OBJECTIVE: To compare the efficacy of proton pump inhibitor vs. ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication. METHODS: Randomized trials comparing 1-week regimens with (i) proton pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was confirmed by histology or 13C-urea breath test at least 4 weeks after therapy. Data sources included PubMed database and abstracts from congresses until October 1999. Statistical analysis was by meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). RESULTS: Twelve studies met the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A, and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A, mean H. pylori eradication efficacy by intention-to-treat analysis (pooled data) was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor, C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on H. pylori eradication was 1.15 (95% CI: 0.8-1.64%). Mean H. pylori eradication with RBC, C and N was 87. 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95% CI: 1.08-2.85%). CONCLUSION: RBC and proton pump inhibitor have similar efficacy for H. pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co-prescribed antibiotics.     

Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin.

Rabeprazole is a potent proton pump inhibitor and is mainly reduced to thioether rabeprazole by a non-enzymatic pathway and partially metabolized to demethylated rabeprazole by CYP2C19 in the liver. We intended to determine a cure rate for Helicobacter pylori infection by dual rabeprazole/amoxicillin therapy in relation to CYP2C19 genotype status prospectively. Ninety-seven patients with gastritis and H. pylori infection completed the dual therapy with 10 mg of rabeprazole bid and 500 mg of amoxicillin tid for 2 weeks. At 1 month after treatment, cure of H. pylori infection was assessed on the basis of histology, a rapid urease test, culture, polymerase chain reaction (PCR), and 13C-urea breath test. CYP2C19 genotype status was determined by a PCR-restriction fragment length polymorphism method. Of the 97 patients, 33 were homozygous extensive metabolizers (homEM), 48 were heterozygous extensive metabolizers (hetEM), and 16 were poor metabolizers (PM). Cure of H. pylori infection was achieved in 79 of the 97 patients (81.4%, 95%CI = 71.9-88.7). Significant differences in cure rates among the homEM, hetEM, and PM groups were observed; 60.6% (95%CI = 42.1-77.3), 91.7% (95%CI = 80.0-97.7), and 93.8% (95%CI = 69.8-99.8), respectively (P = 0.0007). Twelve patients without cure after initial treatment (10 homEMs and 2 hetEMs) were successfully retreated with rabeprazole 10 mg q.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks. The cure rates for H. pylori infection by dual rabeprazole/amoxicillin therapy depended on the CYP2C19 genotype status. This dual therapy appears to be effective for hetEM and PM patients. However, high dose dual rabeprazole/amoxicillin therapy was effective even for homEM patients. Therefore, the genotyping test of CYP2C19 appears to be a clinically useful tool for the optimal dual treatment with rabeprazole plus amoxicillin.     

Meta-analysis: the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication

BACKGROUND: There is much debate about the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre-treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta-analysis. METHODS: The literature was searched in order to identify randomized clinical trials comparing modern triple/quadruple therapies for H. pylori eradication without pre-treatment with a proton pump inhibitor with exactly the same regimen with pre-treatment. The overall risk difference (with - without pre-treatment) was calculated by pooling the risk differences of the individual studies weighted by the inverse of their variances. RESULTS: Nine studies, investigating a total of 773 patients, were identified. There was considerable variation regarding therapy regimen and duration. Pooled eradication rates were 81.3% (312 of 384) for patients with pre-treatment and 81.2% (316 of 389) for patients without pre-treatment. The (weighted) overall risk difference was 0.1% (95% CI: -5%; 5%). CONCLUSION: Pre-treatment with a proton pump inhibitor does not influence H. pylori eradication.     

Review article: esomeprazole in the treatment of Helicobacter pylori

Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori, with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori. Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86-90% and per protocol eradication rates of 90-91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77-78% and per protocol eradication rates of 84-85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori, with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.     

Esomeprazole in the treatment of Helicobacter pylori

Proton pump inhibitor-based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori , with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10-day proton pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S-isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori . Seven-day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat eradication rates of 86–90% and per protocol eradication rates of 90–91% in duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention-to-treat eradication rates of 77–78% and per protocol eradication rates of 84–85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori , with eradication rates comparable to previously studied proton pump inhibitor-based triple therapies.     

艾司奥美拉唑为基础的三联疗法根除幽门螺杆菌的荟萃分析

目的：比较艾司奥美拉唑为基础的和其他质子泵抑制剂(PPI)为基础的三联疗法治疗幽门螺杆菌(Hp)的根除率。方法：通过MEDLINE(1966年1月-2005年6月)和EMBASE(1988年1月-2005年8月)数据库检索公开发表的研究报告,复习检出文章的参考文献,确定有上述2种三联疗法根除Hp,且只有PPI不同的临床随机对照研究进行荟萃分析。按标准提取来源地区、样本数量、研究时间、治疗方案及Hp根除率情况。结果：通过荟萃分析比较,艾司奥美拉唑+克拉霉素+阿莫西林或甲硝唑组成的三联方法,Hp的根除率为82．1％(按意图分析)和86．1％(按试验方案分析),5项质量较高的临床对照研究的Hp的根除率(按意图分析),艾司奥美拉唑为基础的三联疗法Hp的根除率为84．2％,奥美拉唑为82．0％,优势比(OR)为1．17(95％的可信区间：0．88～1．56)。结论：以艾司奥美拉唑为基础的的三联疗法能有效根除Hp,与以奥美拉唑为基础的三联疗法无差异。     

Safety and efficacy of 7-day rabeprazole- and omeprazole-based triple therapy regimens for the eradication of Helicobacter pylori in patients with documented peptic ulcer disease

AIM: A double-blind, randomized study was designed to determine whether rabeprazole- and omeprazole-based triple therapy regimens are therapeutically equivalent in the eradication of Helicobacter pylori. METHODS: Three hundred and forty-five patients with current or previously active peptic ulcer and a positive H. pylori urease test were randomly assigned to receive RCA, OCA, RCM or OCM twice daily for 7 days (R, rabeprazole 20 mg; O, omeprazole 20 mg; C, clarithromycin 500 mg; A, amoxicillin 1000 mg; M, metronidazole 400 mg). H. pylori eradication was documented by negative 13C-urea breath tests at 4 and 12 weeks, and was evaluated using a 2 x 2 factorial design with proton pump inhibitor and antibiotic as factors. RESULTS: Overall eradication rates (per protocol/intention-to-treat) were 87%/77% and 85%/75% with rabeprazole and omeprazole, respectively (not significant). However, a statistical interaction between proton pump inhibitor and antibiotic was identified. RCA produced a somewhat higher eradication rate than OCA (94% vs. 84%; difference, 9.8%; 95% confidence interval, - 0.7% to + 20.4%), whereas RCM produced a lower eradication rate than OCM (79% vs. 86%; difference, 8.1%; 95% confidence interval, - 21.4% to + 5.1%). Ulcer healing rates were > 90% with H. pylori eradication. Each regimen was well tolerated. CONCLUSIONS: Rabeprazole- and omeprazole-based triple therapy regimens are therapeutically equivalent in the eradication of H. pylori and well tolerated. The statistical interaction observed between the proton pump inhibitor and supplementary antibiotic may be due to chance.     

Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics

The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.     

Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori

Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ). PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs. Eradication rates by PPI-based therapies are also affected by this genotype, as well as bacterial resistance to antibiotics. An individualized treatment strategy based on CYP2C19-related pharmacogenetics or pharmacogenomics and bacterial resistance is expected to increase the cure rate of the initial treatment. It is also necessary to recognize that there is a possible drug-drug interaction between some of the drugs used in this treatment regimen.     

Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection and CYP2C19 genetic polymorphism

BACKGROUND: Rabeprazole is a new, potent, proton pump inhibitor. The metabolism of rabeprazole is less dependent on CYP2C19 genetic polymorphism. METHODS: A total of 102 Helicobacter pylori-positive patients with gastric ulcer were randomly allocated to three groups: rabeprazole 10 mg (RAC10), rabeprazole 20 mg (RAC20) or rabeprazole 40 mg (RAC40) plus amoxicillin 750 mg and clarithromycin 200 mg twice daily for 7 days. CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: All-patients-treated-based eradication rates in patients treated with RAC10, RAC20 and RAC40 were 83%, 77% and 90%, respectively, and per protocol-based eradication rates were 83%, 80% and 90%, respectively. The eradication rates in the three groups were not significantly different. There was also no significant difference between the all-patients-treated-based eradication rate in CYP2C19 extensive metabolizers and that in poor metabolizers (86% vs. 77%). Adverse events were 12% in extensive metabolizers and 23% in poor metabolizers, and the difference in these incidence rates was also not statistically significant. CONCLUSIONS: Triple therapy with 10 mg of rabeprazole combined with amoxicillin/clarithromycin is effective for Japanese patients with H. pylori infection, and the H. pylori eradication rate is not affected by CYP2C19 genetic polymorphism.