Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication in real-world clinical practice. METHODS: We retrospectively analyzed data from patients with H. pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H. pylori eradication rate. The secondary endpoint was adverse events. RESULTS: Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P = 0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P = 0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P = 0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P = 0.001). CONCLUSIONS: Tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.

Rational design on loop regions for precisely regulating flexibility of catalytic center to mitigate overoxidation of prazole sulfides by Baeyer-Villiger monooxygenase.

S-omeprazole and R-rabeprazole are important proton pump inhibitors (PPIs) used for treating peptic disorders. They can be biosynthesized from the corresponding sulfide catalyzed by Baeyer-Villiger monooxygenases (BVMOs). During the development of BVMOs for target sulfoxide preparation, stereoselectivity and overoxidation degree are important factors considered most. In the present study, LnPAMO-Mu15 designed previously and TtPAMO from Thermothelomyces thermophilus showed high (S)- and (R)-configuration stereoselectivity respectively towards thioethers. TtPAMO was found to be capable of oxidating omeprazole sulfide (OPS) and rabeprazole sulfide (RPS) into R-omeprazole and R-rabeprazole respectively. However, the overoxidation issue existed and limited the application of TtPAMO in the biosynthesis of sulfoxides. The structural mechanisms for adverse stereoselectivity between LnPAMO-Mu15 and TtPAMO towards OPS and the overoxidation of OPS by TtPAMO were revealed, based on which, TtPAMO was rationally designed focused on the flexibility of loops near catalytic sites. The variant TtPAMO-S482Y was screened out with lowest overoxidation degree towards OPS and RPS due to the decreased flexibility of catalytic center than TtPAMO. The success in this study not only proved the rationality of the overoxidation mechanism proposed in this study but also provided hints for the development of BVMOs towards thioether substrate for corresponding sulfoxide preparation.

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

The effect of food and acid-reducing agents on the pharmacokinetic profile of capivasertib: Results from a randomized, crossover study.

AIMS: This two-part, adaptive study assessed the effect of food and an acid-reducing agent (rabeprazole) on the pharmacokinetics (PK) and safety of capivasertib, a potent AKT inhibitor, in clinical development for cancer treatment. METHODS: In Part 1, healthy participants (n = 24) were randomized to receive single-dose capivasertib after overnight fasting, a high-fat, high-calorie meal and with rabeprazole postovernight fasting in one of six treatment sequences. Based on Part 1 results, a new group of participants (n = 24) were randomized (Part 2) to receive capivasertib after overnight fasting, a low-fat, low-calorie meal and modified fasting (food restricted from 2 h before dosing to 1 h postdose) in one of six treatment sequences. Blood samples were collected for PK analyses. RESULTS: Following a high-fat, high-calorie meal, capivasertib exposure increased versus overnight fasting (geometric mean ratio [GMR] [90% confidence interval (CI)]: area under the concentration-time curve [AUCinf ] 1.32 [1.22, 1.43], maximum concentration [Cmax ] 1.23 [1.08, 1.41]), but was comparable to that postmodified fasting (GMR: AUCinf 1.13 [0.99, 1.29], Cmax 0.85 [0.70, 1.04]). AUCinf was similar and Cmax was lower with/without rabeprazole (GMR: AUCinf 0.94 [0.87, 1.02]), Cmax 0.73 [0.64, 0.84]). Capivasertib exposure was similar after a low-fat, low-calorie meal versus overnight fasting (GMR: AUCinf 1.14 [1.05, 1.25], Cmax 1.21 [0.99, 1.48]) or modified fasting (GMR: AUCinf 0.96 [0.88, 1.05], Cmax 0.86 [0.70, 1.06]). Safety was consistent with that in larger trials. CONCLUSIONS: This study demonstrates that administering capivasertib with food or acid-reducing agents does not lead to clinically relevant PK or safety profile changes.

Network meta-analysis of different dosages of esomeprazole and rabeprazole for the treatment of Helicobacter pylori.

BACKGROUND: The optimal dosage of new generation proton pump inhibitors (PPIs) in increasing cure rate of Helicobacter pylori (H. pylori) infection remains unclear. This network meta-analysis aimed to comprehensively evaluate the comparative efficacy and safety of different dosages of esomeprazole and rabeprazole in treating H. pylori infection. MATERIALS AND METHODS: We searched PubMed, Cochrane Central Registry for Controlled Trials (CENTRAL), and EMBASE for randomized controlled trials (RCTs) involving esomeprazole and rabeprazole with different dosages from their inception through 31 March, 2022. After data extraction and risk of bias assessment, network meta-analyses were conducted using STATA 14.0. We calculated the surface under the cumulative ranking (SUCRA) to rank all regimens. RESULTS: Thirteen studies including 14 reports were included. Six dosages including rabeprazole 10 mg (R10bid), 20 mg (R20bid), and 40 mg (R40bid) twice daily and esomeprazole 20 mg (E20bid) and 40 mg (E40bid) twice daily as well as 40 mg once daily (E40qd) were identified. Network meta-analysis suggested that R40bid ranked highest in the cure rate (83.8%), followed by E40bid (82.6%), E20bid (54.5%), R20bid (34.2%), R10bid (22.8%), and E40qd (22.0%); however, E40qd ranked highest in adverse events (91.1%), followed by R20bid (57.8), R10bid (57.6%), E20bid (38.9%), E40bid (34.2%), and R40bid (20.4%). Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: Based on the available evidence, R40bid and E40bid might be the optimum dosage to increase the cure rate; however, E40qd was superior for adverse events. Nevertheless, future studies should validate the results from this network meta-analysis.

Repurposing rabeprazole sodium as an anti-Clostridium perfringens drug by inhibiting perfringolysin O.

AIMS: Clostridium perfringens infections affect food safety, human health, and the development of the poultry feed industry. Anti-virulence is an alternative strategy to develop new drug. Perfringolysin O (PFO) is an exotoxin of C. perfringens that has been demonstrated to play critical roles in the pathogenesis of this organism, promising it an attractive target to explore drugs to combat C. perfringens infection. METHODS AND RESULTS: Based on an activity-based screening, we identified six PFO inhibitors from the Food and Drug Administration (FDA)-approved drug library, among which rabeprazole sodium (RS) showed an optimal inhibitory effect with an IC50 of 1.82 ± 0.746 µg ml-1. The GLY57, ASP58, SER190, SER193-194, ASN199, GLU204, ASN377, THR379, and ALA200 in PFO interacted with RS during binding based on an energy analysis and H-bond analysis. This interaction blocked the oligomer formation of PFO, thereby inhibiting its cytotoxicity. RS treatment significantly increased the survival rate and alleviated pathological damage in C. perfringens or PFO-treated Galleria mellonella. CONCLUSIONS: RS could potentially be used as a candidate drug for treating C. perfringens infection.

Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3-mediated ZO-1 expression.

Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, the effect of Rabeprazole on gut barrier function remains to be identified. In this study, we show that ZO-1 expression is decreased in patients receiving Rabeprazole by immunofluorescence (IF) analysis. Western blotting (WB) and real-time PCR (qPCR) results demonstrate that Rabeprazole treatment leads to a significant downregulation of ZO-1 expression through inhibition of the FOXF1/STAT3 pathway, leading to destroy barrier function, which illustrates a novel pathway that Rabeprazole regulates barrier function in gastric epithelial cells. Mechanistically, Rabeprazole treatment led to a downregulation of STAT3 and FOXF1 phosphorylation, leading to inhibit nuclear translocation and decrease the binding of STAT3 and FOXF1 to ZO-1 promoter, respectively. Most important, endogenous FOXF1 interacted with STAT3, and this interaction was dramatically abolished by Rabeprazole stimulation. Overexpression of STAT3 and FOXF1 in GES-1 cells reversed the inhibitory effect of Rabeprazole on ZO-1 expression, respectively. These finding extended the function of Rabeprazole and established a previously unappreciated mechanism by which the Rabeprazole/FOXF1/STAT3 axis facilitated ZO-1 expression to regulate barrier function, and a comprehensive consideration and evaluation was required in treatment of patients.

[Comparison of the effectiveness of rabeprazole original and generic products in the monotherapy of gastroesophageal reflux disease].

AIM: To compare the effectiveness of rabeprazole original and generic products in the treatment of gastroesophageal reflux disease (GERD) using impedance-pH monitoring. MATERIALS AND METHODS: Patients (n=35) diagnosed with GERD were divided into two groups. Group 1 patients (n=17, 45.2±1.7 years) received the rabeprazole original product (Pariet) 20 mg/day; Group 2 patients (n=18, 48.1±1.9 years) received 20 mg/day of a generic product. On Day 10 of therapy, all patients underwent 24-hour esophagus impedance-pH monitoring (Ohmega, Medical Measurement Systems, the Netherlands). The percentage of time with pH<4 in the esophagus, the total number and number of acidic, slightly acidic and slightly alkaline gastroesophageal refluxes (GERs), the latency period, and the duration of rabeprazole action were analyzed. The clinical efficacy of the drug was assessed using the GerdQ questionnaire. Statistical data were processed using Microsoft Office 2010 (Excel) and Biostat 2000 software packages. RESULTS: No significant differences were noted between the two groups of patients by gender, age, body mass index, smoking frequency, and GERD type (p>0.05). The average duration of action of the rabeprazole original product was significantly higher than that of the generics (13.2±0.6 and 8.8±0.7 h, respectively, p<0.05). In the rabeprazole original product group, compared to the generics group, the following values were lower: total GERs - 47.0 [43.3; 60.0] and 71.8 [54.3; 95.0], respectively, p<0.05; percentage of time with intraesophageal pH<4 - 1.8 [0.5; 2.3] and 2.1 [0.3; 6.8], respectively, p<0.05; the number of acidic GERs - 4.7 [2.2; 12.0] and 23.3 [12.6; 32.0], respectively, p<0.05. The total GerdQ questionnaire score in Group 1 was significantly lower than in Group 2 (5.4±0.1 vs 6.9±0.4, respectively; p>0.05). CONCLUSION: In treating GERD with the rabeprazole original product compared to generics, a significantly longer duration of acid production suppression, a more pronounced decrease in esophageal acidification, and a more statistically significant clinical improvement were observed.

The protective effect of rabeprazole on cisplatin-induced apoptosis and necroptosis of renal proximal tubular cells.

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.

Identification and genotoxicity evaluation of potential impurities in rabeprazole sodium using in silico and in vitro analyses.

Rabeprazole sodium is a widely used drug for gastrointestinal disorders. Several analytical methods for identifying rabeprazole sodium and its impurities have been reported. However, the genotoxicity of rabeprazole sodium and its impurities is still unclear. Thus, it is necessary to develop analytical methods that can identify the structures of its impurities and evaluate their genotoxicity. Here, we used high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry for identifying the impurities in rabeprazole sodium enteric-coated tablets. Impurities in the samples were matched with synthesized impurities based on the exact mass and secondary mass spectrometry characteristics and then subjected to in silico analysis using the Derek and Sarah software, as well as in vitro genotoxicity evaluations. Our method successfully identified the impurities as 2-[[4-(3-methoxy propane)-3-methyl-N-oxido-2-pyridyl] methyl sulfonyl]-1H-benzimidazole (impurity I), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl]methyl sulfonyl]-benzimidazole (impurity II), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl] methionyl]-1H-benzimidazole (impurity III), and 2-mercapto benzimidazole (impurity IV). In silico analysis predicted that impurity III demonstrated a structural alert; thus, this impurity was evaluated for in vitro genotoxicity using the Ames test and chromosomal aberration assay. Impurity III at concentrations of 7.5-30 µg/mL had an aberration rate of over 5% with or without S-9 mix. Furthermore, impurity III at concentrations of 40-1000 µg/plate significantly increased the number of mutagenic colonies with or without S-9 mix. These results indicated that impurity III should be regulated to the limit of 0.01%.

Clinical observation of magnesium aluminum carbonate combined with rabeprazole-based triple therapy in the treatment of helicobacter pylori-positive gastric ulcer associated with hemorrhage.

Objectives: To evaluate the clinical effect of magnesium aluminum carbonate combined with rabeprazole-based triple therapy in the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. Methods: A total of 80 patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage admitted to the Baoding First Central Hospital from January 2019 to December 2020 were selected and randomly divided into two groups, with 40 cases in each group. The control group were given rabeprazole-based triple therapy, while the experimental group were treated with magnesium aluminum carbonate on the basis of the control group. The changes of symptoms and signs such as abdominal pain, abdominal distension, nausea, vomiting and hematochezia were compared between the two groups before and after treatment. Serological changes of the gastric mucosal microenvironment, such as the serum levels of extracellular regulatory protein kinase (ERK), superoxide dismutase (SOD) and epidermal growth factor receptor (EGFR), were compared between the two groups. Moreover, the differences in the results of gastroscopy between the two groups before and after treatment were compared and analyzed. Results: The scores of gastrointestinal symptoms in the experimental group after treatment were significantly improved compared with the control group (p=0.00). The levels of ERK and EGFR in the experimental group were significantly lower than those in the control group (ERK, p=0.01; EGRF, p=0.00), while the level of SOD was significantly increased (p=0.02). After treatment, the total effective rate of ulcer healing in the experimental group was 82.5%, which was significantly better than 60% in the control group (p=0.03). After treatment, moderate to severe gastric mucosal inflammation in the experimental group decreased to 10%, significantly better than that in the control group (decreased to 30%) (p=0.03). Conclusion: Magnesium aluminum carbonate combined with rabeprazole-based triple therapy is preferred for the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. With such a highly effective treatment regimen, the internal environment and blood supply of gastric mucosal cells can be significantly improved, gastric mucosal inflammation and gastrointestinal symptoms can be ameliorated, and the healing of ulcer surfaces can be accelerated.

A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Although anti-fibrotic treatments, such as pirfenidone, are available that reduce the rate of disease progression, these medications have limitations in tolerability, and IPF patients still have poor prognoses. GDC-3280, an orally available small molecule that was designed to improve upon pirfenidone's activity, has anti-fibrotic activity in animal models. This first-in-human, phase 1 trial evaluated GDC-3280 to determine its safety, tolerability, and pharmacokinetics (PK). METHODS: Single and multiple ascending-doses of GDC-3280 were administered to healthy volunteers in two parts. Part A consisted of 6 treatment groups, each receiving a single, oral dose of GDC-3280 (25-1600 mg) or placebo in the fasted state. Part A also assessed the effect of food and coadministration of a proton pump inhibitor (rabeprazole) on the tolerability and PK of single doses of 400- and 800-mg GDC-3280. Part B consisted of 3 treatment groups who received either 200- or 275-mg GDC-3280 twice daily or 525-mg once daily after a low-fat meal for 7 days. The trial monitored treatment-emergent adverse events (TEAEs) and assessed the pharmacokinetics of GDC-3280 in blood and urine samples. RESULTS: Fifty-six subjects (42 GDC-3280, 14 placebo) in Part A and 24 subjects (18 GDC-3280, 6 placebo) in Part B received treatment. No deaths, serious adverse events, or dose-limiting adverse events occurred, and no subjects withdrew due to a TEAE. In both Parts A and B, most TEAEs were mild. The most frequent TEAEs in Part A were headache and nausea. TEAEs occurred more often when GDC-3280 was administered with food. Pretreatment and coadministration with rabeprazole had no effect on GDC-3280 tolerability. In Part B, the most frequent TEAEs were nausea, dizziness, nasal congestion, and cough. Transient, treatment-related increases in serum creatinine occurred at doses greater than 400 mg in Part A (12%-18% from baseline) and after multiple doses in each group in Part B (20%-34% from baseline). GDC-3280 was generally readily absorbed with a median tmax < 4.0 h following single- or repeat-dose oral administration. In Part A, less-than-dose-proportional increases in systemic exposure occurred, and in Part B, dose-proportional increases occurred within the dose range tested. At doses of 200 mg or lower, more than 50%-70% of orally administered doses were recovered in urine as unchanged GDC-3280 when subjects received a single dose of GDC-3280, suggesting renal excretion is one of the major routes of elimination. Administration of single doses of 400- and 800-mg GDC-3280 after a meal caused statistically significant increases in exposure due to increased rates of absorption compared to the fasted state. Pretreatment and coadministration of rabeprazole dosing led to decreases in exposure compared to GDC-3280 alone, indicating a weak drug-drug interaction. Following repeat dose administration, steady-state plasma concentrations of GDC-3280 were achieved within 2 days with an apparent terminal half-life (t1/2) between 5 and 6 h. CONCLUSIONS: Single and multiple doses of GDC-3280 were generally well tolerated, with acceptable safety and pharmacokinetic profiles that support twice-daily, oral administration with food in future clinical trials.

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.

Rabeprazole-amoxicillin dual therapy as first-line treatment for H pylori eradication in special patients: A retrospective, real-life study.

BACKGROUND: The currently recommended quadruple regimens for Helicobacter pylori infection might not be appropriate for every patient, especially in elderly patients or those with multiple comorbidities. OBJECTIVE: To evaluate the efficacy and safety of rabeprazole-amoxicillin dual therapy in H pylori-positive elderly patients or those with multiple comorbidities. METHODS: From November 2013 to May 2017, the clinical data of H pylori-positive patients ≥60 years old or with multiple comorbidities were collected and reviewed. All patients were given rabeprazole 10 mg three times a day and amoxicillin 1000 mg thrice a day (RA dual therapy) for 14 days as first-line treatment. H pylori eradication was evaluated by 13 C-urea breath test 6 weeks after treatment. Adverse effects were recorded. RESULTS: A total of 198 patients were enrolled, including 116 elderly patients and 82 patients with multiple comorbidities. Successful eradication was achieved in 90.9% (180/198, 95% CI: 86.1%-94.2%) patients. Adverse effects, which were mainly mild (referring to skin rash, abdominal pain, and diarrhea), occurred in 22 patients (22/198, 11.1%) and resolved spontaneously. CONCLUSION: Dual therapy composed of rabeprazole and amoxicillin as a first-line treatment appears to be effective and safe for H pylori infection in elderly patients or those with multiple comorbidities. Additional studies are needed to optimize the regimen.

Searching for an optimal therapy for H pylori eradication: High-dose proton-pump inhibitor dual therapy with amoxicillin vs. standard triple therapy for 14 days.

BACKGROUND & AIMS: We compared a high-dose dual therapy (HDDT) with rabeprazole and amoxicillin and compared it with a standard triple therapy (STT) with rabeprazole, amoxicillin, and clarithromycin for 2 weeks for H pylori eradication in treatment naïve patients. METHODS: H pylori-positive patients were randomly assigned to either a rabeparzole (Pariet) 20 mg b.i.d., amoxicillin (Ospamox) 1 g b.i.d. and clarithromycin (Klacid) 500 mg b.i.d. for 14 days or rabeprazole (Pariet) 20 mg q.i.d., amoxicillin (Ospamox) 1 g q.i.d. also for 14 days. Eradication was tested for by the C13 -UBT at least 4 weeks after the completion of therapy. RESULTS: H pylori was eradicated in 86.2% of patients (81/94) (95% CI: 77.8-91.7) in the STT group compared with 92.8% (90/97) (95% CI: 85.9-96.5) in the HDDT group on ITT analysis. On PP analysis, H pylori was eradicated in 91.0% of patients (81/89) (95% CI: 83.3-95.4) in the STT group compared with 93.8% (90/96) (95% CI: 87.0-97.1) in the HDDT group. Side effects were few although many patients in the STT arm complained of bitter taste. The HDDT arm was well tolerated by patients. CONCLUSIONS: The HDDT gave a high eradication rate comparable to the STT for 2 weeks and was a well-tolerated regimen for H pylori eradication.

Efficacy of a high-dose proton pump inhibitor in patients with gastroesophageal reflux disease: a single center, randomized, open-label trial.

BACKGROUND: The extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established. METHODS: In this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score. RESULTS: Final analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantly higher in the high-dose group than in the standard-dose group (100.0% vs. 84.0%, P = 0.040). For atypical symptoms, the rate of sufficient improvement tended to be higher in the high-dose group than in the standard-dose group (82.4% vs. 63.0%, P = 0.087). Scores of typical and some atypical symptoms (cough and globus) improved after treatment, with significant inter-group differences in time-course changes. CONCLUSIONS: High-dose rabeprazole is more effective for relieving typical GERD symptoms and some atypical symptoms such as cough and globus than a standard-dose regimen. TRIAL REGISTRATION: This research was enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health ( ClinicalTrials.gov Protocol Registration and Results system ID: NCT04001400 ). This study was registered on June 26, 2019 - Retrospectively registered.

Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles.

PURPOSE: Fractional doses of proton pump inhibitors (PPIs) more often than once daily (qd) inhibit 24-h acid secretion more effectively than an increase in the standard single daily dose. Although rabeprazole 5 mg qd is covered for prevention of aspirin-induced gastric injury under the Japanese insurance system, it is unclear whether rabeprazole 5 mg twice daily (bid) would more effectively inhibit acid secretion. We compared acid inhibition between rabeprazole 10 mg qd and 5 mg bid in healthy volunteers with different alleles of CYP2C19. METHODS: Twelve Helicobacter pylori-negative healthy volunteers (CYP2C19 genotypes: extensive metabolizer (EM) (n = 6) and poor metabolizer (PM) (n = 6)) received three kinds of regimen for 7 days under a randomized crossover design: rabeprazole 5 mg qd (5 mg QD), 10 mg qd (10 mg QD), and 5 mg bid (5 mg BID). A 24-hour pH monitoring was conducted before the trial and on day 7 of each regimen. RESULTS: No significant differences in median pH values (4.0 (1.9-5.9)) and (4.4 (2.1-6.5)) or percent time of pH ≥ 4 (50.7% (11.9-86.8%) and 56.8% (19.3-83.9%)) were seen between the 10 mg QD and 5 mg BID regimens. Median pHs and percent time of pH ≥ 4 in CYP2C19 PMs were significantly higher than those in EMs. With 5 mg BID, there was no significant difference in percent-time with pH ≥ 4 between daytime and nighttime, but the 10 mg QD showed a significant difference. CONCLUSION: Rabeprazole 5 mg bid provided no therapeutic advantage for acid inhibition compared with rabeprazole 10 mg qd, regardless of CYP2C19 genotype status.

Influence of rabeprazole and famotidine on pharmacodynamic profile of dual antiplatelet therapy in clopidogrel-sensitive patients: The randomized, prospective, PROTECT trial.

Although acid suppressants are needed to attenuate gastrointestinal bleeding (GIB) after percutaneous coronary intervention (PCI), pharmacodynamic interaction between clopidogrel and proton pump inhibitor (PPI) can increase the risk of high platelet reactivity (HPR). We sought to evaluate serial changes of platelet measures and influence of rabeprazole on platelet measures. After 600-mg clopidogrel loading for elective PCI, clopidogrel-sensitive patients were recruited and randomly assigned to add rabeprazole of daily 20 mg (n = 40) or famotidine of daily 40 mg (n = 40). Platelet measures were performed with light transmittance aggregometry and VASP-P assay. Primary endpoint was 5 µM ADP-induced platelet aggregation (PA) at 30-day follow-up. HPR was defined as 5 µM ADP-induced PA > 46%. Baseline platelet measures did not differ significantly between the groups. The 30-day level of 5 µM ADP-induced PA was similar between the famotidine vs. rabeprazole group (30.0 ± 16.4% vs. 30.2 ± 13.9%, P= .956). In addition, other platelet measures were comparable between the groups. At 30-day follow-up, the incidence of HPR was similar between the famotidine and rabeprazole groups (20.5% vs. 15.4%; P= .555). In conclusion, adjunctive use of rabeprazole showed the similar antiplatelet effect even in clopidogrel-sensitive patients compared with adjunctive famotidine, which may support the similar effect of rabeprazole and famotidine on the antiplatelet effect of dual antiplatelet therapy with clopidogrel plus aspirin.

Multiple widespread fixed drug eruption caused by rabeprazole.

Fixed drug eruption is one of the most common forms of cutaneous adverse drug reactions. Analgesics and antibiotics are the most common drugs causing fixed drug eruption. Here, we report a case of multiple widespread fixed drug eruption caused by rabeprazole.