Mg Of Rabeprazole Research Articles

Rabeprazole: a pharmacologic and clinical review for acid-related disorders

Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of ∼ 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.

Failure of Helicobacter pylori Treatment After Regimes Containing Clarithromycin: New Practical Therapeutic Options

Failure of Helicobacter pylori treatment is a growing problem in daily practice. To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62-93%) in the RLF group and 83% (95% CI: 68-97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65-95%) in the RLF group and 82% (95% CI: 67-96%) in the RBDF group (p= 1.0). Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.

Prokinetics Influence the Pharmacokinetics of Rabeprazole

Background: Proton pump inhibitors (PPIs) are unstable at a low PH. Accelerated transfer of PPIs to the upper small intestine may influence the pharmacokinetics of PPIs. Aim: To see if concomitant use of mosapride citrate with rabeprazole sodium influences the pharmacokinetics of the PPI. Methods: Two-way crossover pharmacokinetic studies were conducted in 9 healthy subjects. 20 mg of rabeprazole was given orally and plasma was obtained before and 1, 2, 3, 4, 5, 6 and 8 h after the dosing. Two weeks later, 5 mg of mosapride was given concomitantly with rabeprazole and plasma was collected as above. The plasma concentrations of rabeprazole were determined by high-performance liquid chromatography. The maximum plasma concentrations (C_max) and the area under the time-plasma concentration curve (AUC) of rabeprazole, and the time to maximum plasma concentration (t_max) were compared in the presence or absence of mosapride. Results: Concomitant use of mosapride resulted in significant increases of mean C_max and mean AUC with ratios of 1.57 and 1.47, respectively. The median t_max changed from 4 to 3 h, although the change was not significant. Conclusions: Mosapride significantly influenced pharmacokinetics of rabeprazole. Co-administration of mosapride could have some favorable effect in PPIs-based therapy.

Efecto del tratamiento erradicador para Helicobacter pylori en pacientes con dispepsia funcional

This study evaluated Helicobacter pylori eradication therapy in terms of symptomatic response in patients with functional dyspepsia. On the other hand, we analyzed the importance of histologic findings as a predictor of treatment response. In particular, we studied whether antral gastritis (which is associated with peptic ulcer) may predict a greater symptomatic response to Helicobacter pylori eradication in functional dyspepsia. This prospective, randomized, single-center trial included 48 patients with functional dyspepsia and Helicobacter pylori infection (27 women and 21 men, mean age 37 +/- 13.5 years). Twenty-seven patients received a 10-day course of rabeprazole, amoxicillin, and clarithromycin (eradication group), followed by 20 mg of rabeprazole for 3 months. Twenty-one patients received 20 mg of rabeprazole for 3 months (control group). Patients were followed up over a 1-year period. All patients completed the Dyspepsia-Related Health Scale Questionnaire, which studies four dimensions: pain intensity, pain disability, non-pain symptoms, and satisfaction with dyspepsia-related health. There was significant symptomatic improvement (p < 0.002) after 6 and 12 months, which was similar with both treatments. In the multivariate analyses, eradication therapy and less severe symptoms before treatment were the only independent factors. The symptomatic response to Helicobacter pylori eradication after 6 months was significantly greater as compared to control therapy (p = 0.01) in patients with antral gastritis and in the non-pain symptoms dimension of the questionnaire. Both treatments proved to be clinically beneficial in patients with functional dyspepsia. We observed a tendency to greater symptomatic benefit with Helicobacter pylori eradication therapy when compared to control treatment in patients with functional dyspepsia and in a population with a high prevalence of this infection. There is a tendency to symptomatic benefit with Helicobacter pylori eradication therapy in patients with antral gastritis.

Failures in a Proton Pump Inhibitor Therapeutic Substitution Program: Lessons Learned

The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy (50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater kappa coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving >/=40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs.

Influence of rabeprazole and lansoprazole on the pharmacokinetics of tacrolimus in relation to CYP2C19, CYP3A5 and MDR1 polymorphisms in renal transplant recipients

The objective of this study was to evaluate whether genetic polymorphisms of CYP2C19, CYP3A5 and MDR1 significantly impact the interaction between tacrolimus and rabeprazole or lansoprazole. Seventy-three recipients were randomly assigned after renal transplantation to receive repeated doses of tacrolimus for 28 days with a regimen of either 20 mg of rabeprazole or 30 mg of lansoprazole. Blood concentrations of tacrolimus were measured by microparticle enzyme immunoassay. The mean daily dose and the dose-adjusted area under the plasma concentration-time curves from 0 to 12 h (AUC(0-12)) of tacrolimus coadministered with rabeprazole or lansoprazole were the lowest and highest, respectively, in CYP2C19 poor metabolizers (PMs) having the CYP3A5*3/*3 genotype (0.084 and 0.112 mg/kg/day and 1.269 and 1.033 ng.h/ml/mg/kg, respectively). On the other hand, the mean dose-adjusted AUC(0-12) of tacrolimus coadministered with rabeprazole or lansoprazole were the highest in CYP2C19 PMs having the MDR13435CC+CT genotype, but not significantly. The present study indicates that there are significant interactions between tacrolimus and rabeprazole or lansoprazole in CYP2C19 PM renal transplant recipients bearing the CYP3A5*3/*3 genotypes. For recipients having these genetic polymorphisms, lower dosages of tacrolimus are required to achieve the target therapeutic index.

Ambulatory Esophageal pH Monitoring Off and on a Proton Pump Inhibitor

Purpose: Ambulatory pH monitoring is the gold standard for the diagnosis of GERD. Whether to perform this test off or on PPI therapy continues to be debated. With the advent of the Bravo pH system, prolonged monitoring sessions have become feasible. Recent data have shown that 96 hour studies using two separate receivers calibrated to one Bravo capsule can effectively document off (first 24 hours) and on (remaining 72 hours) drug response1. While exciting, this approach may not be practical. Most institutions may not have the resources to allocate two receivers for one patient over a 4 day period. We have presented our experience using a standard 48 hour, single receiver, Bravo pH capsule to measure esophageal acid exposure both off and on PPI therapy. Methods: All Bravo pH studies performed at our institution between 12/04 and 4/06 were reviewed. Patients were instructed to withhold PPI for 7 days prior to the study. All Bravo capsules were placed the standard 6 cm above the squamocolumnar junction. During the first 24 hours, the patient remained off a PPI. The patient was then instructed to take either 40 mg of rabeprazole or 80 mg of esomeprazole by mouth. This dose was repeated 12 hours later. The percent of time that pH was less than 4 over 24 hours (% time pH<4) was the primary variable examined. Total number of refluxes over a 24 hour period was also considered. Day 1 vs. day 2 values were compared using the Wilcoxon signed-rank test. Results: Fifty-four studies were reviewed. One study was removed as the capsule was radiologically shown to have detached and fallen into the gastric chamber during the study period. Three studies had a% time pH<4 nine standard deviations above the mean and were therefore excluded. The mean% time pH<4 was significantly lower on day 2 (2.68%) as compared to day 1 (5.49%) (p= 0.003). The total number of refluxes per 24 hours was also significantly reduced (34.4 vs. 54.2) (p= 0.004). Conclusions: We have shown that it is feasible to evaluate esophageal acid exposure both off and on PPI therapy during a single 48 hour Bravo pH study. By giving a high dose of a rapid acting PPI on day 2, the esophageal acid exposure can be significantly reduced. This may be more practical than performing two separate studies or a single prolonged study using multiple receivers.

Clarithromycin-Resistant Genotypes and Eradication of Helicobacter pylori

Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. Post hoc subgroup study from a multicenter, randomized trial. Two hospitals in central and southern Italy between January and December 2001. 156 patients with H. pylori infection. Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (70 euros per patient). The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

Rabeprazole: the role of proton pump inhibitors in Helicobacter pylori eradication

Proton pump inhibitors have become one of the cornerstones in the treatment of Helicobacter pylori infection. Rabeprazole (Pariet®) is a substituted benzimidazole proton pump inhibitor with potent gastric acid suppression properties. Its high acid–base dissociation constant allows activation over a broader pH range, resulting in quick, irreversible binding to the H+/K+-ATPase pump, and a more rapid onset of action compared with omeprazole, lansoprazole and pantoprazole. Unlike other proton pump inhibitors, the metabolism of rabeprazole is primarily via a nonenzymatic reduction to the thioether derivative, and the cytochrome P450 isoenzyme 2C19 is only partly involved in its metabolism. The effect of genetic polymorphism in cytochrome P450 isoenzyme 2C19 on the pharmacokinetics and pharmacodynamics of rabeprazole is therefore limited. In humans, once-daily dosing of 5–40 mg of rabeprazole inhibits gastric acid secretion in a dose-dependent manner. In vitro studies have shown that rabeprazole possesses more potent antibacterial properties against the growth of H. pylori than other proton pump inhibitors. Furthermore, its thioether derivative has more potent inhibitory in vitro activity against the growth and motility of clarithromycin-resistant H. pylori than other proton pump inhibitors or commonly used antimicrobials. Despite these inherent favorable characteristics of rabeprazole, randomized controlled trials have largely shown equivalence amongst proton pump inhibitors when used with two antibiotics in the eradication of H. pylori, with cure rates of 75–89% on an intent-to-treat basis. However, rabeprazole appears to consistently achieve such comparable eradication rates even when used at reduced doses (10 mg twice daily) as part of clarithromycin-based triple therapy.

A Comparative Study on Endoscopic Ulcer Healing of Omeprazole Versus Rabeprazole with Respect to CYP2C19 Genotypic Differences

Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, while rabeprazole is mainly nonenzymatically degraded with a minor involvement by CYP2C19. We investigated the gastric ulcer healing effect of omeprazole versus rabeprazole evaluated endoscopically with reference to the different CYP2C19 genotypes. Eighty patients with active gastric ulcer were treated with a daily dose of 20 mg of omeprazole or 10 mg of rabeprazole. The endoscopic evaluation was performed at the baseline and 2- and 8-week posttreatment periods. The endoscopic improvement of gastric ulcer size and ulcer healing rates using a thin rubber disc with a diameter of 6 mm, were evaluated in relation to the CYP2C19 genotypic status. The mean 2-week posttreatment ulcer size value by rabeprazole did not significantly differ among the different CYP2C19 genotypes, whereas the mean value in the homozygous extensive metabolizer patients treated with omeprazole was significantly (P = 0.0057) greater than in those with rabeprazole. However, after the 8-week treatment, omeprazole and rabeprazole showed the similarly high healing rates of 87.8% (31/37) and 88.9% (32/36), respectively. Although both omeprazole and rabeprazole showed a high healing rate of gastric ulcer after the 8-week treatment period, the healing effect of rabeprazole appears to be relatively independent of the CYP2C19 status, resulting in an earlier repair of gastric mucosal damage evaluated endoscopically compared to that of omeprazole.

Efficacy of rabeprazole in patients with reflux esophagitis: A single-center, open-label, practice-based, postmarketing surveillance investigation

Background: The efficacy of rabeprazole sodium 20 mg/d for the treatment of reflux esophagitis has been demonstrated in several studies in Japan. However, studies of rabeprazole sodium 10 mg/d are lacking. Objective: This study was conducted to assess the efficacy and tolerability of rabeprazole 10 mg/d for the treatment of reflux esophagitis. Methods: Patients diagnosed with reflux esophagitis in routine clinical practice were enrolled in this single-center, open-label, practice-based, post-marketing surveillance investigation. Patients were to receive 10 mg of rabeprazole once daily for 8 weeks. The efficacy of rabeprazole was assessed on the basis of symptoms and endoscopic findings in accordance with the modified Los Angeles classification. Tolerability was assessed using subjective symptoms recorded before, during, and after treatment. Results: Of a total of 61 patients enrolled in this study, 47 (77%; 29 men, 18 women; mean age, 63 years) were included in the efficacy and tolerability analyses. Fourteen (23%) patients, including 5 (8.2%) patients who were treated with rabeprazole 20 mg/d, were excluded from the analyses. Endoscopic examinations were performed before and after treatment in 32 of 47 (68.1%) patients; mucosal lesions were healed in 20 of 32 (62.5%) patients after rabeprazole treatment. In patients with mild mucosal lesions prior to treatment, complete remission was achieved in 17 of 24 (70.8%) patients after treatment. Rates of improvement of symptoms were as follows: epigastralgia, 76%; heartburn, 76.7%; dull pain in the esophagus, 86.7%; and belching, 72.2%. Rabeprazole was well tolerated throughout the study; no serious symptomatic adverse events were reported. Although 1 case each of elevated alkaline phosphatase and gamma-glutamyltranspeptidase levels were reported, these changes were mild and improved after continuous treatment with rabeprazole. Conclusion: In this study, rabeprazole 10 mg/d was well tolerated and was shown to have satisfactory efficacy in the healing of esophagitis and the relief of the symptoms of esophagitis.

Rabeprazole in nonerosive gastroesophageal reflux disease: a randomized placebo-controlled trial

OBJECTIVES: Clinical results to date suggest that antisecretory therapy may be less effective in providing symptom relief for patients with nonerosive gastroesophageal reflux disease (GERD) than for patients with erosive disease. This study was carried out to assess the efficacy and rapidity of once-daily rabeprazole (10 mg or 20 mg) in relieving symptoms in endoscopically negative patients with moderately severe GERD symptoms and to evaluate the safety of these doses over 4 wk. METHODS: This placebo-controlled, double blind study enrolled 203 men and women with moderately severe symptoms of GERD. After a 2-wk, single-blind placebo run-in phase, patients were randomized to receive 10 mg or 20 mg of rabeprazole or placebo once daily for 4 wk. RESULTS: Rabeprazole rapidly and effectively relieved heartburn, with significant improvements on day 1 of dosing. It also improved most other GERD-related symptoms, including regurgitation, belching, bloating, early satiety, and nausea. Both rabeprazole doses were significantly superior to the placebo with respect to time to the first 24-h heartburn-free interval (2.5 and 4.5 days for 10 mg and 20 mg of rabeprazole, respectively, vs 21.5 days for the placebo) and first daytime or nighttime heartburn-free interval (1.5–3 days for rabeprazole groups vs 12.5–15 days for the placebo), as well as to percentage of time patients were heartburn-free and free of antacid use. Both rabeprazole doses were well tolerated. CONCLUSIONS: Based on these findings and prior studies, rabeprazole reliably relieves GI symptoms equally well in both nonerosive GERD and erosive GERD.

Rabeprazole for the prevention of pathologic and symptomatic relapse of erosive or ulcerative gastroesophageal reflux disease

OBJECTIVE: We evaluated the effectiveness and safety profile of 10 and 20 mg of rabeprazole, a new proton pump inhibitor, once daily versus placebo in preventing endoscopic and symptomatic relapse for up to 1 yr among patients with healed erosive or ulcerative gastroesophageal reflux disease (GERD). METHODS: The 52-wk trial used a multicenter, randomized, double-blind, parallel-group design in which 209 men and women were assigned to 10 or 20 mg of rabeprazole once daily in the morning or placebo. RESULTS: Both rabeprazole doses were significantly superior to placebo in preventing endoscopic relapse ( p < 0.001), and 20 mg was significantly more effective than 10 mg ( p < 0.04). Both doses were also significantly superior to placebo in reducing the frequency and severity of heartburn relapse ( p < 0.001). When adjusted for differences in exposure to study medication, no significant differences were found in the incidence of adverse events. No clinically significant changes were found regarding clinical laboratory parameters, vital signs, electrocardiograms, ophthalmological evaluations, body weight, serum gastrin, and enterochromaffin-like cell histology. CONCLUSIONS: Once-daily therapy with 10 or 20 mg of rabeprazole effectively prevents pathological and symptomatic GERD relapse. The 20-mg dose is significantly more effective than the 10-mg dose in preventing endoscopic recurrence. Treatment was well tolerated, and no clinically significant safety findings emerged. Our findings support rabeprazole’s efficacy in preventing GERD recurrence with excellent tolerability and a short-term favorable safety profile.

Rabeprazole for the prevention of pathologic and symptomatic relapse of erosive or ulcerative gastroesophageal reflux disease

We evaluated the effectiveness and safety profile of 10 and 20 mg of rabeprazole, a new proton pump inhibitor, once daily versus placebo in preventing endoscopic and symptomatic relapse for up to 1 yr among patients with healed erosive or ulcerative gastroesophageal reflux disease (GERD). The 52-wk trial used a multicenter, randomized, double-blind, parallel-group design in which 209 men and women were assigned to 10 or 20 mg of rabeprazole once daily in the morning or placebo. Both rabeprazole doses were significantly superior to placebo in preventing endoscopic relapse (p < 0.001), and 20 mg was significantly more effective than 10 mg (p < 0.04). Both doses were also significantly superior to placebo in reducing the frequency and severity of heartburn relapse (p < 0.001). When adjusted for differences in exposure to study medication, no significant differences were found in the incidence of adverse events. No clinically significant changes were found regarding clinical laboratory parameters, vital signs, electrocardiograms, ophthalmological evaluations, body weight, serum gastrin, and enterochromaffin-like cell histology. Once-daily therapy with 10 or 20 mg of rabeprazole effectively prevents pathological and symptomatic GERD relapse. The 20-mg dose is significantly more effective than the 10-mg dose in preventing endoscopic recurrence. Treatment was well tolerated, and no clinically significant safety findings emerged. Our findings support rabeprazole's efficacy in preventing GERD recurrence with excellent tolerability and a short-term favorable safety profile.

Effects of genetic differences in CYP2C19 status on cure rates of Hericobacter pylori infection by dual rabeprazole/amoxicillin therapy in comparison with dual omeprazole/amoxicillin therapy

Backgrounds and Aims: Omeprazole (OPZ) is mainly metabolized by S-mephenytoin 4' -hydroxylase (CYP2CI9) in the liver. On the other hand, rabeprazole (RPZ), a new proton pump inhibitor, is mainly metabolized to thioether-RPZ by non-enzymatic pathway and partially metabolized to demethylated-RPZ by CYP2CI9 in the liver. The therapeutic effect of OPZ is more affected by genetic differences in CYP2C19 status than that of RPZ. This study aimed to determine whether CYP2CI9 genotype status is associated with the eradication rate of Helicobacterpylori (Hp) by a dual RPZlamoxicillin (AMPC) therapy in comparison with a dual OPVAMPC therapy. Methods: 140 patients with Hp positive-peptic ulcer or gastritis were treated with daily doses of 20 mg of RPZ (n=70) or OPZ (n =70) and 1.5-2.0g of AMPC for two weeks. CYP2C19 genotype status for two mutations associated with the poor metabolizer phenotype, CYP2C19ml in exon 5 (ml) and CYP2C19m2 in exon 4 (m2), was determined by a PCR-RFLP method. One month after treatment, eradication rates of Hp were determined on the basis of histology, culture, RUT, 13C-UBT and PCR (J Clin Microbiol1996; 34: 2421-5). Results: Patients were classified into three groups on the basis of CYP2C19 genotyping test results; homEM group (homozygous for the wild-type alleles in both exon 5 and exon 4 [wt/wtj), hetEM group (heterozygous for CYP2C19ml or for CYP2C19m2 [wtlml or wtlm2]), and PM group (heterozygous for the CYP2C19ml and CYP2C19m2 or homozygous for CYP2C19ml [mllm2 or ml/ml]). The eradication rates by a dual RPZlAMPC therapy versus a dual OPVAMPC therapies in different genotype groups were 63.6% (8114) vs 31.0% (9/29) in homEM groups (p=0.0261), 89.5% (34/38)vs 62.1% (18129) in het EM groups (p=0.0160), and 90.0% (9/10) vs 91.6% (11/12) in PM groups (p>0.2). Moreover, the cure rate by the dual RPVAMPC therapy in the hetEM plus PM groups (mutation-positive group) was 89.6% (43/48). Conclusion: The eradication rates by both dual OPZlAMPC therapy and RPZlAMPC were affected by CYP2C19 genotype status. However, the eradcation rate by dual RPZIAMPC therapy was higher than that of dual OPZlAMPC therapy. Moreover, in hetEM and PM patients, the dual RPZIAMPC therapy yielded a sufficiently high eradication rate without second antibiotics, such as clarithromycin or metronidazole. The genotyping test of CYP2C 19 appears to be a useful clinical tool for the optimal selection of PPls. 2662

Ｒａｂｅｐｒａｚｏｌｅおよびｔｅｐｒｅｎｏｎｅのｐｉｒｏｘｉｃａｍによる胃十二指腸粘膜傷害予防効果

The effect of teprenone, a cytoprotective agent and rabeprazole, a proton pump inhibitor (PPI), in preventive mucosal damages caused by piroxicam was evaluated in a controlled prospective study in 30 rheumatic patients requiring NSAIDs. Piroxicam capsules at a clinical standard dose of 20 mg/day were administered in 30 patients for 2 weeks and 20 patients were randomly assigned to receive either rabeprazole 10 mg once daily or teprenone 3 times daily for 2 weeks, along with piroxicam. Gastric damage was slightly less tendency in teprenone group compared with the only administered piroxicam group. However, duodenal ulcers developed in 2 cases in both groups with no intergroup difference in preventive effect. Among 10 patients given 10 mg of rabeprazole along with piroxicam, there was a significantly lower incidence of development of gastroduodenal damage in rabeprazole administered group compared with patients given only piroxicam, which suggested that PPI is as effective in suppressing NSAID induced acute gastroduodenal lesions.

Review article: the pharmacology of rabeprazole.

Rabeprazole sodium is a new substituted benzimidazole proton pump inhibitor with several differences compared with existing proton pump inhibitors. In vitro and animal studies have demonstrated that rabeprazole is a more potent inhibitor of H+,K(+)-ATPase and acid secretion than omeprazole, and is a more rapid inhibitor of proton pumps than omeprazole, lansoprazole, or pantoprazole. This probably reflects rabeprazole's faster activation in the parietal cell canaliculus. In human studies, once-daily doses of 5-40 mg of rabeprazole inhibit gastric acid secretion in a dose-dependent fashion. A once-daily dose of 20 mg has consistently achieved profound decreases in 24-h intragastric acidity in single and repeat dosing studies, in healthy volunteers and patients with either peptic ulcer disease or gastro-oesophageal reflux disease. Significantly greater decreases in intragastric acidity are achieved on day 1 of dosing with rabeprazole 20 mg than with omeprazole 20 mg. As with other proton pump inhibitors, rabeprazole has in vitro antibacterial activity against Helicobacter pylori, with greater activity against this organism than either lansoprazole or omeprazole. In addition to inhibiting bacterial urease activity, rabeprazole binds to several molecules on H. pylori. Clinical trials are needed to assess the clinical importance of these findings, as well as to assess whether the potential advantages of rabeprazole result in clinical benefit for patients with acid-related diseases.