Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

AIM: To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs). METHODS: Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe). RESULTS: The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION: Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.

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 allocated to the combination therapy group 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. and TGF-beta 1, 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. and TGF-beta 1, 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. to collagen. 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.

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.

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%.

Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression

AIM： To study the effect of proton pump inhibitor （PPI） treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor （EGFR） expression. METHODS： After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole （n = 24） or 40 mg esomeprazole （n = 22） therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. RESULTS： Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. CONCLUSION： Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

Esomeprazole tablet vs omeprazole capsule in treating erosive esophagitis

AIM: Esomeprazole, an oral S-form of omeprazole, has been a greater acid inhibitor over omeprazole in treating acid-related diseases. Only less published data is available to confirm its efficacy for Asian people. Therefore, a perspective, double-blind, randomized comparison of esomeprazole tablets 40 mg (Nexium(?)) vs omeprazole capsules 20 mg (Losec(?)) in treating Chinese subjects with erosive/ulcerative reflux esophagitis (EE) was conducted. METHODS: A total of 48 EE patients were enrolled and randomized into two treatment groups under 8-wk therapy: 25 receiving esomeprazole, while another 23 receiving omeprazole treatment. Finally, 44 completed the whole 8-wk therapy. RESULTS: The difference in healing EE between two groups was 22.7% (72.7% vs 50.0%), not reaching significant value (P = 0.204). The median of the first time needed in relieving heartburn sensation was 1 d for both groups and the remission rates for heartburn on the 1st d after treatment were 77.3% and 65%, respectively (NS). The scores of various reflux relieving symptoms evaluated either by patients or by investigators were not different. Regarding drug safety, 28% of esomeprazole group and 26.1% of omeprazole group reported at least one episode of adverse effects, while constipation and skin dryness were the common side effects in both groups (NS). CONCLUSION: Esomeprazole 40 mg is an effective and safe drug at least comparable to omeprazole in treating Chinese EE patients.

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.

Comparison of esomeprazole enteric-coated capsules vs esomeprazole magnesium in the treatment of active duodenal ulcer: A randomized, double-blind, controlled study

AIM： To evaluate the efficacy and tolerability of two different preparations of esomeprazole in healing duodenal ulcers. METHODS： A total of 60 patients with active duodenal ulcers were enrolled and randomized to receive esomeprazole enteric-coated capsules （40 mg） or esomeprazole magnesium （40 mg）, once daily, for 4 consecutive wk, with ulcer healing being monitored by endoscopy. Safety and tolerability were also assessed. RESULTS： Fifty seven patients completed the whole trial. The ulcer healing rates at the end of wk 2 were 86.7% and 85.2% in the esomeprazole enteric-coated capsules and esomeprazole magnesium groups, respectively （P = 0.8410）, and reached 100% at the end of wk 4 in beth groups. Symptom relief at the end of wk 2 was 90.8% in the esomeprazole enteric-coated capsules group and 86.7% in the esomeprazole magnesium group （P = 0.5406）; at the end of wk 4 symptom relief was 95.2% and 93.2%, respectively （P = 0.5786）. Adverse events occurred in 16.7% of the esomeprazole entericcoated capsules group and 14.8% of the esomeprazole magnesium group （P = 1.0000）. CONCLUSION： The efficacies of esomeprazole entericcoated capsules and esomeprazole magnesium in healing duodenal ulcer lesions and relieving gastrointestinal symptoms are equivalent. The tolerability and safety of beth drugs were comparable.

Development and validation of a high throughput UPLC–MS/MS method for simultaneous quantification of esomeprazole,rabeprazole and levosulpiride in human plasma

A high throughput ultra pressure liquid chromatography-mass spectrometry （UPLC-MS/MS） method with good sensitivity and selectivity has been developed and validated for simultaneous quantification of esomeprazole, rabeprazole and levosulpiride in human plasma using lansoprazole as internal standard （IS）. The extraction method based on liquid-liquid extraction technique was used to extract the analytes and IS from of 50 μL of human plasma using methyl tert-butyl ether：ethyl acetate （80：20, v/v）, which offers a high recovery. Chromatographic separation of analytes and IS was achieved on a Hypersil gold C18 column using gradient mobile phase consisting of 2 mM ammonium formate/acetonitrile. The flow rate was set at 0.5 mL/min to elute all the analytes and IS within 1.00 min runtime. Detection of target compounds was performed on a triple quadruple mass spectrometer by multiple reaction monitoring （MRM） mode via positive electrospray ionization （ESI）. Method validation results demonstrated that the developed method has good precision and accuracy over the concentration ranges of 0.1-2000 ng/mL for each analyte. Stability of compounds was established in a battery of stability studies, i.e., bench top, autosampler, dry extract and long-term storage stability as well as freeze-thaw cycles. The validated method has been successfully applied to analyze human plasma samples for application in pharmaco- kinetic studies.

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.

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）。

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。

The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients

Purpose： To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. Methods： A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups： 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Results： Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively （p 〈 0.05）, the hemostatic time was 22.10 h ± 5.18 h and 28.27 h ± 5.96 h, respectively （p 〈 0.05）. Conclusion： Both doses of intravenous esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease

Background The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease （GERD） on proton-pump inhibitor （PPI） therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.Methods GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH＋ group did not.Results Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% （52/58） of symptom-free patients and 67% （12/18） of symptom-persistent patients achieved esophageal pH normalization after therapy （P=0.030）. The mean post-therapy gastric nocturnal percent time of pH 〈4.0 was significantly higher in pH＋group than that in pH- group （P 〈0.001） after therapy. The multivariate regression analysis identified hiatus hernia （P〈0.001） and persistent reflux symptom （P=0.004） were two independent factors predicting the low post-therapy esophageal pH level.Conclusions Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse.Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

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.

CYP2C19 polymorphism influences Helicobacter pylori eradication

The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1&#x003b2;- 511 polymorphism) would be also under consideration.

Two-week treatment with proton pump inhibitor is sufficient for healing post endoscopic submucosal dissection ulcers

AIM: To investigate the optimum period of treatment for post endoscopic submucosal dissection (ESD) ulcers.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(H.pylori) eradication.METHODS:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two H.pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei DG.H.pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy.Compliance and tolerability of regimens were also assessed.RESULTS:H.pylori eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe effects.CONCLUSION:Third-line levofloxacin-doxycycline triple therapy had a low H.pylori eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.