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...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.展开更多
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 allo...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.展开更多
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 ...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.展开更多
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)....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.展开更多
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, ra...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.展开更多
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 characteris...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.展开更多
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 c...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.展开更多
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 patie...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.展开更多
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. The...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, randomizedcomparison of esomeprazole tablets 40 mg (Nexium (R)) vs omeprazole capsules 20 mg (Losec(R)) 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 groupreported 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.展开更多
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 info...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 = 14) or 40 mg esomeprazole (n = 12) 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 p53expression 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.展开更多
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 rece...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 both 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 enteric-coated capsules group and 14.8% of the esomeprazole magnesium group (P = 1.0000). CONCLUSION: The efficacies of esomeprazole enteric-coated capsules and esomeprazole magnesium in healing duodenal ulcer lesions and relieving gastrointestinal symptoms are equivalent. The tolerability and safety of both drugs were comparable.展开更多
基金Supported by Research Grant of Kitasato Institute Hospital
文摘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.
文摘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.
文摘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.
基金Supported by Research Foundation of Chang Gung Memorial Hospital,No.CMRPG8D1441
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by the Research Foundation of Digestive Medicine,Taiwan, China
文摘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, randomizedcomparison of esomeprazole tablets 40 mg (Nexium (R)) vs omeprazole capsules 20 mg (Losec(R)) 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 groupreported 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.
基金Supported by the National Science Foundation (OTKA Grant No:T 034345)
文摘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 = 14) or 40 mg esomeprazole (n = 12) 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 p53expression 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.
文摘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 both 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 enteric-coated capsules group and 14.8% of the esomeprazole magnesium group (P = 1.0000). CONCLUSION: The efficacies of esomeprazole enteric-coated capsules and esomeprazole magnesium in healing duodenal ulcer lesions and relieving gastrointestinal symptoms are equivalent. The tolerability and safety of both drugs were comparable.