BACKGROUND::

Scant data exist on the normal range of serum gastrin in infants. In phase I and III trials of rabeprazole in gastroesophageal reflux disease (GERD), we studied serum gastrin levels in infants 1-11 months old, and assessed normal ranges and the effect of acid-suppressive drugs.

METHODS::

Overall, 349 treatment naïve or treatment-experienced (previously exposed to proton pump inhibitors [PPIs] and/or H2-receptor antagonists [H2RAs]) infants with GERD were screened for baseline serum gastrin. Repeat gastrin was monitored at early termination or end of study (EOS), allowing assessment of 1-8 week daily rabeprazole (5- or 10-mg) treatment on gastrin levels.

RESULTS::

Median (5%-95% range) baseline gastrin was 118 (39-315) ng/L in the treatment-naïve group (n = 251), driven mostly by high levels (121.5 [48-326] ng/L) in the 1-<4 month old subgroup. Treatment-experienced infants (n = 98) had elevated baseline gastrin levels (152 [48-487] ng/L; P = 0.0011) with no clear difference between previously PPI-exposed and H2RA-exposed groups. At EOS, mean (SD) levels were unchanged from baseline in infants withdrawn from rabeprazole to placebo (124 [94] ng/L), but elevated from baseline in those continuing treatment with 5-mg (245 [151] ng/L) and 10-mg (332 [222] ng/L) rabeprazole during the study.

CONCLUSION:

: Gastrin levels in treatment-naïve infants were elevated through 8 months of age. Between 8 and 12 months of age, they declined so that the median level was within the upper limit of the normal adult range (<100 ng/L). Previous exposure to acid suppressive medications and short-term exposure to rabeprazole significantly increased gastrin levels in infants <1 year old.

BACKGROUNDAIMS: The aim of this study was to evaluate the efficacy and cost efficiency of omeprazole 10 mg and rabeprazole 10 mg once daily for 24 weeks in the maintenance therapy.This was a randomized, open-label study enrolling 279 patients with erosive esophagitis A or B (Los Angeles classification) and typical gastroesophageal reflux disease symptoms. Patients who showed complete endoscopic and symptomatic healing after 8 weeks of proton pump inhibitor treatment were randomly allocated to maintenance treatment with omeprazole 10 mg once daily or rabeprazole 10 mg once daily for 42 weeks. The primary efficacy endpoint was the proportion of patients with symptomatic remission at 42 weeks.At the end of 42 weeks of maintenance therapy, 96.4% of omeprazole and 95.1% of rabeprazole treated patients remained symptom free (P > 0.05). Two drugs were also comparable with regard to the severity and frequency of reflux symptoms during the maintenance phase (P > 0.05). By the cost-minimization analysis, the mean total costs per patient for remaining symptom-free for 6 months were 241,775 won for omeprazole and 287,115 won for rabeprazole, respectively.Omeprazole 10 mg appeared to have similar efficacy in maintaining symptomatic remission as rabeprazole 10 mg, but was superior to rabeprazole 10 mg in terms of cost efficiency in the maintenance therapy of gastroesophageal reflux disease symptoms.

There are inconsistent conclusions about whether CYP2C19 variants could affect H. pylori eradication rate in patients treated with the proton pump inhibitor (PPI)-based therapy. We therefore performed a meta-analysis of randomized clinical trials (RCTs) to re-evaluate the impact of CYP2C19 variants on PPI-based triple therapy for the above indication.All relevant RCTs in the PubMed, Cochrane Library, EMBASE, Web of Science and two Chinese databases (up to February 2013) were systematically searched, and a pooled analysis was performed with the odds ratio (OR) and 95% confidence interval (CI) by the STATA software.Sixteen RCT datasets derived from 3680 patients were included. There was no significant heterogeneity across the data available in this meta-analysis. There were significant differences in that rate between homozygous (HomEMs) and heterozygous (HetEMs) extensive metabolizers (OR 0.724; 95% CI 0.594-0.881), between HomEMs and poor metabolizers (PM) (OR 0.507; 95%CI 0.379-0.679), or between HetEMs and PMs (OR 0.688; 95%CI 0.515-0.920), regardless of the PPI being taken. Furthermore, sub-analysis of individual PPIs was carried out to explore the difference across all the PPIs used. A significantly low rate was seen in HomEMs vs. HetEMs taking either omeprazole (OR 0.329; 95%CI 0.195-0.553) or lansoprazole (OR 0.692; 95%CI 0.485-0.988), and also in HomEMs vs. PMs for omeprazole (OR 0.232; 95%CI 0.105-0.515) or lansoprazole (OR 0.441; 95%CI 0.252-0.771). However, there was no significant difference between HetEMs and PMs taking either one. No significant differences were observed for rabeprazole or esomeprazole across the CYP2C19 genotypes of interest.Carriage of CYP2C19 loss-of-function variants is associated with increased H. pylori eradication rate in patients taking PPI-based triple therapies when omeprazole or lansoprazole is chosen. However, there is no a class effect after use of rabeprazole or esomeprazole.

Enantioresolution of four anti-ulcer drugs (chiral sulfoxides), namely, omeprazole, rabeprazole, lansoprazole and pantoprazole, was carried out by high-performance liquid chromatography using a polysaccharide-based chiral stationary phase consisting of monochloromethylated cellulose (Lux cellulose-2) under normal and polar-organic-phase conditions with ultraviolet detection at 285 nm. The method was validated for linearity, accuracy, precision, robustness and limit of detection. The optimized enantioresolution method was compared for both the elution modes. The optimized method was further utilized to check the enantiomeric purity of dexrabeprazole. Copyright © 2013 John Wiley & Sons, Ltd.

Clarithromycin and rabeprazole are both valued for their safety profile. Very few cases of adverse side-effects related to these drugs, when given individually, have been reported; serious side-effects of clarithromycin in combination with rabeprazole have never been reported. The present case reports on a 51-year-old woman with gastritis who received clarithromycin combined with rabeprazole for Helicobacter pylori infection. After taking 500 mg clarithromycin and 10 mg rabeprazole orally she displayed acute psychotic symptoms of dissociative disorder, including: impairment of orientation and attention; the feeling of dreaming; disintegration of thinking; stereotyped speech; flattened emotion; amnesia. Routine blood investigations, computed tomography scans and electroencephalography showed no abnormalities. All symptoms disappeared without antipsychotic treatment ≈ 48 h after she had taken the two drugs. Combining clarithromycin with rabeprazole might increase the risk of neurotoxicity, particularly in susceptible individuals. This should be a concern in clinical practice.

Gastroesophageal reflux disease is a diversity disease that affects life quality of people in the world. Due to the complicated pathogenesis and variations in clinical manifestations, there is still no true gold standard for GERD diagnosis, and it is still difficult to diagnose this disease in some patients. The proton pump inhibitor's diagnostic test (the PPI test) is noninvasive, of low cost, tied to treatment, and widely accepted. Our aim is to evaluate the diagnostic significance of coapplying a rabeprazole test with the SF-36 for GERD in this study. Our study shows that the SF-36 in combination with the rabeprazole test can screen GERD patients and increase the sensitivity and specificity of GERD diagnosis through reference to the change in SF-36 score before and after the treatment (65 in the trial).

ABSTRACT

Introduction: Despite adequate treatment with proton pump inhibitors (PPIs), symptoms of gastroesophageal reflux disease (GERD) may remain persistent as well as Barrett's esophagus may emerge. It may be proposed that the relaxant effect of PPIs on the smooth muscles may lead to resistance of symptoms. The aim of this study is to investigate effects of rabeprazole on the lower esophageal sphincter (LES) pressure with a rat model. Materials and

Methods:

Sixteen rats were grouped as control and treatment groups. After obtaining LES tissues followed by a 60 min equilibration period for stabilization, contractile response to carbachol was obtained by application of single dose of carbachol to have a final concentration of 10(-6) M in the organ bath. After the contractions reached a plateau, concentration-response relationships for rabeprazole were obtained in a cumulative manner in the treatment group.

Results:

In the carbachol contracted LES preparations; 1.5 × 10(-6) and 1.5×10(-5) M of rabeprazole caused 6.08% and 11.34% relaxations respectively which were not statistically significant. However, mean integral relaxation value for 4.5 × 10(-5) M of rabeprazole was 17.34% and this relaxation was significant compared with controls.

Conclusions:

In the present study, rabeprazole caused no direct significant change in LES tone in the therapeutic dose range applied to the organ bath. However, rabeprazole at the high dose caused a significant decrease in the LES tone.

Proton pump inhibitors (PPIs) have become some of the most frequently prescribed medications for treatment of adults and children. Their effectiveness for treatment of peptic conditions in the pediatric population, including gastric ulcers, gastroesophageal reflux disease (GERD), and Helicobacter pylori infections has been established for children older than 1 year. Studies of the preverbal population of neonates and infants have identified doses that inhibit acid production, but the effectiveness of PPIs in the treatment of GERD has not been established except for the recent approval of esomeprazole treatment of erosive esophagitis in infants. Reasons that have been proposed for this are complex, ranging from GERD not occurring in this population to a lack of histologic identification of esophagitis related to GERD to questions about the validity of symptom scoring systems to identify esophagitis when it occurs in infants. The effectiveness of PPIs relates to their structures, which must undergo acidic activation within the parietal cell to allow the PPI to be ionized and form covalent disulfide bonds with cysteines of the H(+)-K(+)-adenosine triphosphatase (H(+)-K(+)-ATPase). Once the PPI binds to the proton pump, the pump is inactivated. Some PPIs, such as omeprazole and rabeprazole bind to cysteines that are exposed, and their binding can be reversed. After irreversible chemical inhibition of the proton pump, such as occurs with pantoprazole, the recovery of the protein of the pump has a half-life of around 50 h. Cytochrome P450 (CYP) 2C19 and to a lesser degree CYP3A4 clear the PPIs metabolically. These enzymes are immature at birth and reach adult levels of activity by 5-6 months after birth. This parallels studies of the maturation of CYP2C19 to adult levels by roughly the same age after birth. Specific single nucleotide polymorphisms of CYP2C19 reduce clearance proportionally and increase exposure and prolong proton pump inhibition. Prolonged treatment of pediatric patients with PPIs has not caused cancer or significant abnormalities.

To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital.In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g., gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use).Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that supports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication.AST is overused in hospitalized non-critically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.

The aim of this study is to investigate the effect of CYP2C19 polymorphism and co-therapy with rabeprazole or esomeprazole on the anti-platelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and *3, and vasodilator stimulated phosphoprotein (VASP) testing to measure platelet reactivity index (PRI). 239 consecutive patients were enrolled: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). 45 patients had loss of function polymorphism (LOF) (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean platelet reactivity index (PRI) was 20.7±21.9% in the C group, 19.1±20.9% in the CR group, and 24.5±22.9% in the CE group (p= NS). High-on-treatment Platelet Reactivity (HPR), defined as PRI>50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE respectively (p=NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor PPI co-therapy were associated with HPR. The use of PPIs was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.