Rabeprazole is an effective proton pump inhibitor to treat acid‐related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC‐MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 μm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid‐acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 → 242.2 and 346.1 → 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL−1, the intra‐run precisions were below 5.4%, the inter‐run precisions were below 9.9%, and the accuracy was between −9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)‐(+)‐ and (S)‐(−)‐rabeprazole after oral administration of 10‐mg rabeprazole sodium enteric‐coated tablet in healthy Chinese subjects.
Summary Background Proton pump inhibitors (PPIs) are widely used for the treatment of acid‐related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium‐competitive acid blockers. Vonoprazan may thus be an alternative to PPIs. Aim To evaluate efficacy, rapidity and duration of acid‐inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype. Methods In this randomised, open‐label, two‐period cross‐over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH. Results Acid‐inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2–33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2–40.4]. The Day 1 to Day 7 ratio of 24‐h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation. Conclusions This study demonstrated a more rapid and sustained acid‐inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid‐related diseases.
Summary Background Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid‐related diseases. Aim To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. Methods Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. Results In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6–6.4), 5.7 (4.1–7.4), 6.6 (4.9–8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2–100.0%)], irrespective to CYP2C19 genotype. Conclusion Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night‐time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.
Summary Background H. pylori eradication failures are difficult to treat and rescue therapies often consist of complex treatment regimens. Aim To determine an effective and practical rescue therapeutic strategy for H. pylori treatment failures using two consecutive regimens: first rescue therapy ‐ rabeprazole 20 mg t.d.s. and amoxicillin 1 g t.d.s. for 2 weeks and for failures a further second rescue therapy ‐ rabeprazole 20 mg b.d., levofloxacin 500 mg b.d., amoxicillin 1 g b.d. for a further 2 weeks. Methods Consecutive patients who failed the proton pump inhibitor (PPI) 1‐week triple therapy were recruited for the study. H. pylori status was determined by a C13 urea breath test. Results One hundred and forty‐nine patients received the first rescue therapy. Seven were not compliant to medication/defaulted follow‐up. Eradication success‐ first rescue therapy: per protocol (PP) analysis‐107/142 (75.4%) (95% CI (68.3–82.4%) and intention to treat (ITT) analysis‐107/149 (71.8%) 95% CI (64.6–79.0%). Thirty‐one of 35 patients who failed the first rescue therapy received the second rescue therapy. All were compliant with medications. Eradication success‐ PP and ITT was 28/31 (90.3%) 95% CI (74.2–98.0%). The cumulative eradication rate using both rescue therapies: PP analysis‐ 135/138 (97.8%) 95% CI: (93.8–99.6%), ITT analysis‐ 135/149 (90.6%) 95% CI: (84.7–94.8%). Conclusions A 2‐week high dose PPI‐amoxicillin dual therapy followed by a PPI‐amoxicillin‐levofloxacin triple therapy were highly successful in achieving eradication in H. pylori treatment failures.
Several retrospective studies have shown that the antitumor efficacy of capecitabine-containing chemotherapy decreases when co-administered with a proton pump inhibitor (PPI). Although a reduction in capecitabine absorption by PPIs was proposed as the underlying mechanism, the effects of PPIs on capecitabine pharmacokinetics remain unclear. We prospectively examined the effects of rabeprazole on the pharmacokinetics of capecitabine and its metabolites.We enrolled patients administered adjuvant capecitabine plus oxaliplatin (CapeOX) for postoperative colorectal cancer (CRC) patients and metastatic CRC patients receiving CapeOX with/without bevacizumab. Patients receiving a PPI before registration were allocated to the rabeprazole group, and the PPI was changed to rabeprazole (20 mg/day) at least 1 week before the initiation of capecitabine treatment. On day 1, oral capecitabine (1000 mg/m2) was administered 1 h after rabeprazole intake. Oxaliplatin (and bevacizumab) administration on day 1 was shifted to day 2 for pharmacokinetic analysis of the first capecitabine dose. Plasma concentrations of capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine, and 5-fluorouracil were analyzed by high-performance liquid chromatography. Effects of rabeprazole on inhibition of cell proliferation by each capecitabine metabolite were examined with colon cancer cells (COLO205 and HCT116).Five and 9 patients enrolled between September 2017 and July 2018 were allocated to rabeprazole and control groups, respectively. No significant effects of rabeprazole on area under the plasma concentration–time curve divided by capecitabine dose for capecitabine and its three metabolites were observed. Rabeprazole did not affect the proliferation inhibition of colon cancer cells by the respective capecitabine metabolites.Rabeprazole does not affect capecitabine pharmacokinetics.
► Rabeprazole sulfide showed good inhibition efficiency for mild steel in 0.5M H2SO4. ► It acts as mixed type inhibitor. ► Follows Langmuir adsorption isotherm and zero order kinetics. ► Evaluation by chemical, electrochemical and quantum chemical methods. The inhibition effect of Rabeprazole sulfide (2-[[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]-methylthio]-1H-benzimidazole) (RS) on the corrosion behavior of mild steel in 0.5M H2SO4 solution was studied by weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurements. Polarization measurements indicate that RS act as a mixed type inhibitor. The adsorption of RS on the mild steel surface follow Langmuir adsorption isotherm model and zero order kinetics. The thermodynamic parameters governing the adsorption process were determined and discussed. Also, quantum chemical parameters were calculated to provide further insight into the mechanism of inhibition action of RS.
Summary Background The decreasing efficacy of H. pylori eradication treatments over time makes the search for better regimens and adjuvant medications a priority. Aim To conduct a meta‐analysis of studies comparing rabeprazole or esomeprazole with other proton pump inhibitors (PPI) or with each other in H. pylori eradication treatment. Methods Selection of Studies: Randomised clinical trials comparing esomeprazole or rabeprazole with first‐generation PPIs (omeprazole‐lansoprazole‐pantoprazole) or with each other. Results The meta‐analysis (35 studies, 5998 patients) showed higher eradication rates for esomeprazole than for first‐generation PPIs: 82.3% vs. 77.6%; OR = 1.32(1.01–1.73); NNT = 21. Rabeprazole also showed better results than first‐generation PPIs: 80.5% vs. 76.2%; OR = 1.21(1.02–1.42); NNT = 23. PPI dosage sub‐analysis: only esomeprazole 40 mg b.d. improved results [83.5% esomeprazole vs. 72.4% first generation; OR = 2.27(1.07–4.82); NNT = 9]. Whereas rabeprazole 10 and 20 mg b.d. maintained results, esomeprazole 20 mg b.d. obtained lower efficacy. Esomeprazole vs. rabeprazole sub‐analysis (five studies): no significant differences were found: 78.7% vs. 76.7%; OR = 0.90(0.70–1.17). CYP2C19 sub‐analysis: Genotype did not significantly affect eradication either in first [OR = 1.76(0.99–3.12)] or new generation [OR = 1.19(0.73–1.95)] PPIs. However, sub‐analysis considering only extensive metaboliser patients showed higher eradication with new‐generation PPIs [OR = 1.37(1.02–1.84)]. Conclusions Esomeprazole and rabeprazole show better overall H. pylori eradication rates than first‐generation PPIs. This clinical benefit is more pronounced in esomeprazole 40 mg b.d. regimens. In CYP2C19 extensive metabolisers, new‐generation PPIs are more effective than first‐generation PPIs for H. pylori eradication. However, a general recommendation of using new‐generation PPIs in all scenarios remains unclear.
The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to varying degree by several cytochrome P450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The principal isoenzymes involved in the metabolism of proton pump inhibitors are CYP2C19 and CYP3A4. Of these two, minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of the proton pump inhibitors. The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism. Recent studies have brought to light the important role that this polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid‐related diseases.
Aliment Pharmacol Ther 2011; 33: 845–854 Summary Background Novel rabeprazole extended‐release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients. Aim To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole‐ER formulations vs. esomeprazole 40 mg and rabeprazole delayed‐release (DR) 20 mg. Methods Helicobacter pylori‐negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty‐four‐hour intragastric pH was monitored on days −1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5. Results A total of 248 subjects (N = 31/group) were enrolled in the study. On day 5, rabeprazole‐ER groups provided mean durations of 18.5–20.2 h (77.0–84.1% of 24‐h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24‐h) and rabeprazole‐DR 20 mg (15.2 h/63.2% of 24‐h). A similar increase was observed on day 1. While percentage of daytime (8 am–10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night‐time (10 pm‐8 am) with intragastric pH >4.0 was higher with the rabeprazole‐ER groups (57.0–72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole‐DR 20 mg (34.0%). Conclusion Rabeprazole‐ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole‐DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night‐time; this was supported by the extended‐release phamacokinetic characteristics.