First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ^(13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years(male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen(PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry(UMIN000009642).RESULTS: The H. pylori eradication rates by EPZbased triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors(PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer(EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM(P < 0.05). The serum PG?Ⅰ?level and PG?Ⅰ/Ⅱ ratio were significantly increased after eradication of H. pylori(P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZbased triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other firstgeneration PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other firstgeneration PPIs.

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study

AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly alloc at e d t o t he c ombinat ion t he r apy gr oup or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor Ⅷ and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group(P < 0.05). There were significant differences(P < 0.05) in collagen deposition, expression level of Factor Ⅷ and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group(P < 0.05). The ratio of collagen?Ⅰ?to collagen Ⅲ was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group(P < 0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa.

Comparative study of esomeprazole and lansoprazole in triple therapy for eradication of Helicobacter pylori in Japan

AIM:To evaluate the efficacy and safety of esomeprazole-based triple therapy compared with lansoprazole therapy as first-line eradication therapy for patients with Helicobacter pylori(H.pylori)in usual post-marketing use in Japan,where the clarithromycin(CAM)resistance rate is 30%.METHODS:For this multicenter,randomized,openlabel,non-inferiority trial,we recruited patients(≥20years of age)with H.pylori infection from 20 hospitals in Japan.We randomly allocated patients to esomeprazole therapy(esomeprazole 20 mg,CAM 400 mg,amoxicillin(AC)750 mg for the first 7 d,with all drugs given twice daily)or lansoprazole therapy(lansoprazole30 mg,CAM 400 mg,AC 750 mg for the first 7 d,with all drugs given twice daily)using a minimization method with age,sex,and institution as adjustment factors.Our primary outcome was the eradication rate by intention-to-treat(ITT)and per-protocol(PP)analyses.H.pylori eradication was confirmed by a urea breath test from 4 to 8 wk after cessation of therapy.RESULTS:ITT analysis revealed the eradication rates of 69.4%(95%CI:61.2%-76.6%)for esomeprazole therapy and 73.9%(95%CI:65.9%-80.6%)for lansoprazole therapy(P=0.4982).PP analysis showed eradication rate of 76.9%(95%CI:68.6%-83.5%)for esomeprazole therapy and 79.8%(95%CI:71.9%-86.0%)for lansoprazole therapy(P=0.6423).There were no differences in adverse effects between the two therapies.CONCLUSION:Esomeprazole showed non-inferiority and safety in a 7 day-triple therapy for eradication of H.pylori compared with lansoprazole.

First-week clinical responses to dexlansoprazole 60 mg and esomeprazole 40 mg for the treatment of grades A and B gastroesophageal reflux disease

AIM To compare the one-week clinical effects of single doses of dexlansoprazole and esomeprazole on grades A and B erosive esophagitis.METHODS We enrolled 175 adult patients with gastroesophageal reflux disease(GERD). The patients were randomized in a 1:1 ratio into two sequence groups to define the order in which they received single doses of dexlansoprazole(n = 88) and esomeprazole(n = 87) for an intention-to-treat analysis. The primary endpoints were the complete symptom resolution(CSR) rates at days 1, 3, and 7 after drug administration.RESULTS Thirteen patients were lost to follow-up, resulting in 81 patients in each group for the per-protocol analysis. The CSRs for both groups were similar at days 1, 3 and 7. In the subgroup analysis, the female patients achieved higher CSRs in the dexlansoprazole group than in the esomeprazole group at day 3(38.3% vs 18.4%, P = 0.046). An increasing trend toward a higher CSR was observed in the dexlansoprazole group at day 7(55.3% vs 36.8%, P = 0.09). In the esomeprazole group, female sex was a negative predictive factor for CSR on post-administration day 1 [OR =-1.249 ± 0.543; 95%CI: 0.287(0.099-0.832), P = 0.022] and day 3 [OR =-1.254 ± 0.519; 95%CI: 0.285(0.103-0.789), P = 0.016]. Patients with spicy food eating habits achieved lower CSRs on day 1 [37.3% vs 21.4%, OR =-0.969 ± 0.438; 95%CI: 0.380(0.161-0.896), P = 0.027]. CONCLUSION The overall CSR for GERD patients was similar at days 1-7 for both the dexlansoprazole and esomeprazole groups, although a higher incidence of CSR was observed on day 3 in female patients who received a single dose of dexlansoprazole.

Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects

BACKGROUND The pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied.AIM To evaluate the pharmacokinetic characteristics of esomeprazole magnesium(Eso)enteric-coated capsule in the healthy subjects in China and the bioequivalence of the two formulations.METHODS This study was conducted in the Phase I Clinical Trial Unit of the Affiliated Hospital of Changchun University of Chinese Medicine.A total of 64 healthy subjects were enrolled in the study.Thirty-two subjects fasted or fed,took the test or reference formulation Eso enteric-coated capsule by a four-cycle,two-sequence crossover of fasting/fed,self-controlled method.The liquid chromatographymass spectrometry was performed to determine the drug plasma concentration at 16 different time points within 12 h after drug administration.The pharmacokinetic parameters Cmax,area under the curve(AUC)0-t,and AUC0-inf were calculated to evaluate the bioequivalence.RESULTS Pharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting status.The ratio of geometric means of Cmax was 104.15%,with a confidence interval(CI)of 98.20-110.46%.The ratio of geometric means of AUC0-t was 105.26%,with a CI of 99.80-111.01%.The ratio of geometric means of AUC0-inf was 105.37%,with a CI of 99.97-111.06%.The pharmacokinetic parameters were also evaluated after subjects took the reference formulation of Eso enteric-coated capsule after eating.The upper limit of 95%CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state Cmax was-0.1689,and the point estimate was 0.9509(0.80-1.25).The upper limit of 95%CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-t was-0.1015(≤0),and the point estimate was 0.9003(0.80-1.25).The upper limit of 95%CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-inf was-0.0593(≤0),and the point estimate was 0.8453(0.80-1.25).The results indicated that the two formulations were bioequivalent under both fasting and fed states.CONCLUSION The two types of esomeprazole tablets were bioequivalent under both fasting and fed states,and both were generally well tolerated.

Esomeprazole regimens for reflux symptoms in Chinesepatients with chronic gastrit

AIM To compare symptom control with esomeprazoleregimens for non-erosive reflux disease and chronicgastritis in patients with a negative endoscopy.METHODS： This randomized, open-label study wasdesigned in line with clinical practice in China. Patientswith typical reflux symptoms for ≥ 3 mo and a negativeendoscopy who had a Gastroesophageal Reflux DiseaseQuestionnaire score ≥ 8 were randomized to initialtreatment with esomeprazole 20 mg once daily eitherfor 8 wk or for 2 wk. Patients with symptom reliefcould enter another 24 wk of maintenance/on-demandtreatment, where further courses of esomeprazole 20mg once daily were given if symptoms recurred. Theprimary endpoint was the symptom control rate at week24 of the maintenance/on-demand treatment period.Secondary endpoints were symptom relief rate, successrate （defined as patients who had symptom reliefafter initial treatment and after 24 wk of maintenancetreatment）, time-to-first-relapse and satisfaction rate.RESULTS： Based on the data collected in the modifiedintention-to-treat population （MITT; patients in the ITTpopulation with symptom relief after initial esomeprazoletreatment, n = 262）, the symptom control rate showeda small but statistically significant difference in favorof the 8-wk regimen （94.9% vs 87.3%, P = 0.0473）.Among the secondary endpoints, based on the datacollected in the ITT population （n = 305）, the 8-wkgroup presented marginally better results in symptomrelief after initial esomeprazole treatment （88.3% vs83.4%, P = 0.2513） and success rate over the wholestudy （83.8% vs 72.8%, P = 0.0258）. The 8-wkregimen was found to provide a 46% reduction in riskof relapse vs the 2-wk regimen （HR = 0.543; 95%CI：0.388-0.761）. In addition, fewer unscheduled visits andhigher patient satisfaction supported the therapeuticbenefits of the 8-wk regimen over the 2-wk regimen.Safety was comparable between the two groups, withboth regimens being well tolerated.CONCLUSION： Chinese patients diagnosed withchronic gastritis achieved marginally better control ofreflux symptoms with an 8-wk vs a 2-wk esomeprazoleregimen, with a similar safety profile.

Esomeprazole治疗GERD优于雷尼替丁

挪威和瑞典的研究人员称，在预防胃一食管返流性疾病（EERD）症状复发方面，按要求和连续给予esomeprazole（Ⅰ）方案都比连续给予雷尼替丁（ranitidine）（Ⅱ）效价比好。

阿司匹林联合esomeprazole治疗预防再出血

最新研究发现．阿司匹林联合esomeprazole治疗预防阿司匹林导致的溃疡出血患者发生再出血的效果要优于氯吡格雷（clopidogrel）。

Research Progress of Esomeprazole and its Potential Risk for Administration

Esomeprazole,one of the proton pump inhibitors(PPIs),has been widely used in acid-related diseases,such as gastro-esophageal reflux disease and Helicobacter pylori infection.Compared with other PPIs,esomeprazole has higher acid control efficiency,bioavailability,stability,and less interindividual variation depending on its pharmacokinetic properties.Esomeprazole was considered safe for long-term administration.However,several recent studies have contradicted its absolute safety,and some detrimental cases have been reported in some special groups,such as pregnant women and patients with liver cirrhosis.Because acid-related diseases usually require long-term therapy and esomeprazole inhibits CYP2C19 enzyme that increases the probability of drug-drug interaction,these risks have become a concern.Recent studies have shown that esomeprazole not only inhibits acid secretion,but also exhibits acid-independent effects in inflammatory conditions.Esomeprazole can modulate NF-κb activation to resist tissue oxidation and apoptosis in gastric ulcer.In CCL4-induced liver fibrosis,esomeprazole improves oxidative stress,fibrogenesis,and apoptosis,but the mechanism still remains unclear.This review summarized the property of esomeprazole and its potential risk for administration,and its latest research progress,which may facilitate clinicians to better use and avoid the potential risks.

Observation on the Clinical Effect of Emergency Interventional Therapy on Acute Severe Non- Variceal Upper Gastrointestinal Bleeding

Objective:To observe the clinical effect of emergency interventional therapy for patients with acute severe non-variceal upper gastrointestinal bleeding.Methods:78 patients with acute severe non-variceal upper gastrointestinal bleeding who were treated in the General Hospital of the Eastern Theater Command from May 2020 to May 2023 were randomly divided into two groups according to different treatment plans.The study group underwent emergency upper gastrointestinal angiography and interventional embolization therapy,the control group was treated with esomeprazole;the clinical data related to the two groups were compared,including the total effective rate of treatment,blood pressure stabilization time,bleeding control time,etc.Results:The effective rate of clinical treatment in the study group was 97.44%,which was higher than that in the control group,which was 79.49%(P<0.05).Both were significantly shorter(P<0.05);the 7 d rebleeding rate and 30 d rebleeding rate of the study group were lower than those of the control group(P<0.05);the 7 d and 30 d mortality rates of the two groups after treatment were compared,and the comparative study group was lower,but there was no significant difference(P>0.05).Conclusion:Emergency interventional therapy can control bleeding more quickly,shorten bleeding control time and complete hemostasis time,shorten blood pressure stabilization time and abdominal pain relief time,and reduce rebleeding rate in patients with acute severe non-variceal upper gastrointestinal bleeding.

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.

FDA宣布埃索美拉唑和奥美拉唑不会增加心血管事件风险

曾有2项研究资料提示，严重胃食道反流性疾病患者长期使用埃索美拉唑（esomeprazole，Nexium）或奥美拉唑（omeprazole．Prilosec）可能增加心血管事件风险。对此，FDA对这2个药物进行了安全审查。2007年12月，FDA宣布审查结果说，没有证据表明埃索美拉唑和奥美拉唑会增加心血管事件的风险。

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

Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.

替那拉唑治疗顽固性反流的潜力

据《胃消化药理学和治疗学》杂志(March 15th，p655)的报道，一项对Negma—Lerads／Mitsubishi's(三菱)公司的长效质子泵抑制剂(PPIs)——替托拉唑(暂译名，tentoprazole)的Ⅰ期临床表明，该药比阿斯利康公司的艾美拉唑(暂译名，esomeprazole，Nexium)更能有效减少夜间胃酸骤增的发生。公司预期于2004年开展该药的Ⅲ期临床研究。

AstraZeneca向欧盟递交Axanum的申请

AstraZeneca公司向欧洲管理当局提交固定剂量复方制剂Axanum（20mg esomeprazole／81mg阿司匹林）（Ⅰ）的新药申请。

两种药物治疗阿司匹林导致的溃疡出血效果更好

一项最新研究表明，对需要一种抗血小板药物预防血管性疾病但又具有阿司匹林导致的溃疡出血病史的患者来说，选择阿司匹林与esomeprazole的联合治疗似乎比单独使用氯吡格雷(clopidogrel)的疗效更好。

肌肉骨骼系统用药—AstraZeneca向欧盟提交Vimovo的上市申请

AstraZeneca公司已经向欧盟提交了Vimovo（Ⅰ）作为治疗骨关节病和类风湿关节炎和强直性脊柱炎症状和体征药物的上市许可申请。 （Ⅰ）是由肠溶包衣的萘普生和速释的esomeprazole组成的复方制剂，前者是可缓解疼痛的非甾体抗炎药（NSAID），后者是一种质子泵抑制剂（PPI）。