The onset of antisecretory activity of rabeprazole is faster than that of omeprazole.

This study was performed to compare the efficacy of short-term rabeprazole-based triple therapy with that of omeprazole-based triple therapy and to determine the influence of omeprazole pretreatment in omeprazole-based short-term triple therapy.

This was a 2-center, open-label, prospective, randomized study. Patients who tested positive for Helicobacter (formerly Campylobacter) pylori were randomized to one of three 5-day regimens: (1) rabeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID (RAC group); (2) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID without omeprazole pretreatment (OAC1 group); and (3) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID with 5 days of omeprazole pretreatment 20 mg BID (OAC2 group). Eradication was assessed by (13)C-urea breath test and rapid urease test ∼1 month after completion of treatment. All patients who entered this study were included in the intent-to-treat (ITT) analysis, patients who completed the study were included in the per-protocol (PP) analysis, and patients who did not undergo the (13)C-urea breath test and rapid urease test were included in the all-patients-treated (APT) analysis.

A total of 120 patients (86 men, 34 women; mean [SD] age, 55.8 [14.3] years; range, 19-86 years) were assigned to the RAC, OAC1, or OAC2 group (40 patients in each group). ITT, PP, and APT eradication rates in the RAC group were 90%, 92%, and 90%, respectively; in the OAC1 group, 75%, 83%, and 75%; and in the OAC2 group, 85%, 90%, and 87%. These eradication rates were not significantly different between groups.

Eradication rates did not differ significantly between the three 5-day proton pump inhibitor-based triple therapies in this study population. However, 5-day rabeprazole-based triple therapy tends to be more effective than 5-day omeprazole-based triple therapy in the eradication of H pylori, and treatment with omeprazole before eradication therapy may improve the eradication rates of 5-day omeprazole-based therapy.

The absorption and bioavailability of proton pump inhibitors is influenced by food intake. Proton pump inhibitors bind to the parietal cell active proton pump, which is maximally stimulated after dinner: usually the largest meal of the day. However, it has not been fully clarified whether the efficacy of proton pump inhibitors differs between post-breakfast and pre-dinner dosing.

To perform a pH-monitoring study to clarify this issue for two low-dose proton pump inhibitors.

The subjects were 20 healthy male volunteers (seven Helicobacter pylori-positive and 13 H. pylori-negative), who were divided into two groups of 10 and administered 15 mg lansoprazole or 10 mg rabeprazole, respectively. All subjects underwent ambulatory intragastric 24-h pH- monitoring under three conditions allocated randomly: (i) without medication, (ii) seventh day of post-breakfast administration and (iii) eighth day of pre-dinner administration of each drug.

There was no significant difference in the percentage time during which pH > or =4.0 in the 24-h period between post-breakfast and pre-dinner administration of both drugs (56.6% vs. 55.8%; P = 0.557), although intragastric acidity during administration of both drugs was significantly lower than that without medication.

The timing of drug administration does not significantly influence the efficacy of low-dose proton pump inhibitors.

The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD).

Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test.

Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux.

The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

The attenuated anti-secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whether Helicobacter pylori infection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine.

To investigate the occurrence of the tolerance phenomenon in subjects with and without H. pylori infection during the continuous administration of lafutidine and famotidine.

Subjects were 20 healthy male volunteers (seven H. pylori positive and 13 H. pylori negative cases). All subjects were examined by ambulatory intragastric pH monitoring five times without medication, on the first and 15th day of the administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a cross-over fashion.

The tolerance phenomenon was not observed in H. pylori-positive subjects during the 15-day-long administration of both H2RAs. In contrast, the tolerance phenomenon was observed in H. pylori negative subjects, which has been previously reported.

This study demonstrated that H. pylori infection affects the tolerance phenomenon during continuous administration of H2RAs.

Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI).

Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe).

The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens.

Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.

To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro-mucosal inflammation after eradication.

Two hundred and six H. pylori-positive patients with active gastric ulcer underwent 8-week based therapy (OA) consisting of 2-week amoxicillin with omeprazole and subsequent 6-week omeprazole. They randomly received either rebamipide (OA-R) or placebo (OA-P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically.

Per Protocol Set analysis showed no significant difference in eradication rate between OA-R (64.6%; 95% confidence interval, 54.3-75.0%) and OA-P (67.9%; 95% CI, 57.6-78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA-R (1.84 +/- 0.41) compared with that in OA-P (2.02 +/- 0.39) after 16-weeks of treatment. This suppressive effect on inflammation was observed even in the OA-R patients unsuccessfully eradicated.

Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.

Eradication therapy has been incorporated into clinical practice. The regimens currently recommended for first-line treatment include a 2-week bismuth-based triple therapy (mainly in developing countries), a 1 - 2 week proton pump inhibitor (PPI)-based triple therapy and a 1-week ranitidine bismuth citrate (RBC)-based triple therapy. However, these regimens fail to eradicate Helicobacter pylori in up to 20% of patients due to poor compliance, inadequate treatment duration, smoking, old age and bacterial resistance to nitroimidazoles and/or macrolides in particular. Therefore, alternative regimens that avoid nitroimidazoles and/or macrolides or overcome bacterial resistance to these drugs, improve compliance, minimise side effects and/or reduce costs have been evaluated. One-week quadruple therapy, which adds a PPI or histamine receptor 2-blocker to bismuth-based triple therapy, usually achieves an eradication rate of 90% when used as an alternative first-line therapy but the efficacy decreases when used as a rescue therapy. Several new triple therapies that may be used as alternative and/or rescue therapies have been evaluated. Among these are furazolidone-based (furazolidone plus an antibiotic and a bismuth salt, a PPI or RBC), fluoroquinolone-based (levofloxacin or moxifloxacin plus an antibiotic and a PPI) and ecabet sodium-based (ecabet plus two antibiotics) triple therapies. Recently, rifabutin has been used in combination with a PPI and amoxycillin as a rescue therapy, with satisfactory eradication rates. In addition, a number of new antimicrobial agents are currently under investigation in in vitro studies but the clinical values of these agents needs to be confirmed.

Triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are the present gold standards for cure of Helicobacter pylori infection. However, primary resistance to either clarithromycin or nitroimidazole derivatives is increasing and alternative therapies are needed.

To determine the efficacy and safety of three regimens consisting of amoxicillin and tetracycline or doxycycline combined with either lansoprazole or ranitidine bismuth citrate.

Two hundred and seventy H. pylori infected patients were randomly given one of the following treatments: amoxicillin 1 g twice a day (b.i.d.) plus tetracycline 500 mg four times a day (q.i.d.) with either lansoprazole 30 mg b.i.d. (group LAT) or ranitidine bismuth citrate 400 mg b.i.d. (group RBCAT) for 7 days and amoxicillin 1 g b.i.d. plus doxycycline 100 mg b.i.d. and lansoprazole 30 mg b.i.d. for 14 days (group LAD). Eradication rate was assessed by UBT at 4-6 weeks after therapy.

The three groups (LAT, RBCAT, and LAD) of patients achieved eradication rates of 35% (25-45), 20% (12-29) and 36% (25-46), respectively, on intention-to-treat analysis. Patient compliance was optimal and side-effects minimal in all three groups.

Although the amoxicillin/tetracycline combination is attractive (inexpensive, safe, and with low primary resistance rate), it can not be recommended for H. pylori eradication.

Current standard treatment regimens for Helicobacter pylori infection provide eradication rates 80 to 90%. These rates have been achieved with a variety of 1-week triple therapies using two antibiotics and an acid suppressant. Antibiotic resistance, which may develop during failed treatment, is becoming increasingly common and has led to studies of new regimens for primary therapy, and new strategies for salvage of failed therapy. Other regimens have been designed and tested with the aim of decreasing the cost of initial therapy or to improve compliance, but abbreviated regimens have high incidence of failure and may add to the problem of resistance. Increasing attention has been paid to the need for, and timing of, the determination of antibiotic resistance of H. pylori isolates either at the time of initial diagnosis or after treatment failure. New, simpler, and noninvasive methods are offered for follow-up to determine if eradication has been successful. Treatment regimens should be chosen based on local drug susceptibility patterns and the availability of approved therapeutic agents in each country. Established indications for testing for H. pylori and administering therapy include active or inactive peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, as well as hyperplastic polyps, hyperplastic gastropathy, postendoscopic resection for gastric malignancy, and acute H. pylori gastritis. It is now largely accepted that noninvestigated dyspepsia is an indication for testing for and treating H. pylori, but that dyspeptic symptoms shown not to be associated with ulcer (nonulcer dyspepsia) do not now provide an indication for testing. Controversial or unresolved indications for testing and treating include planned use of chronic antisecretory therapy, planned use of nonsteroidal anti-inflammatory drugs, and use as a general approach to the prevention of gastric cancer.

The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori.

To evaluate the efficacy and safety of ecabet sodium-based eradication of H. pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study.

A total of 120 H. pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s. and clarithromycin 400 mg b.d. (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients). Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment.

One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test. Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91%. There were no significant differences in cure rate or adverse events between the two regimens.

Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.