Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs. Potassium-competitive acid blockers (P-CABs) were developed and have beneficial effects including rapid, long-lasting, and reversible inhibition of the gastric hydrogen potassium ATPase, the proton pump of the stomach. Vonoprazan was recently innovated as a novel, orally active P-CAB. It is currently indicated for the treatment of gastric and duodenal ulcers, reflux esophagitis, and prevention of low-dose aspirin- or nonsteroidal anti-inflammatory drug-related gastric and duodenal ulcer recurrence in Japan. Vonoprazan does not require enteric coating as it is acid-stable, and it can be taken without food because it is quickly absorbed. Vonoprazan accumulates in parietal cells under both acidic and neutral conditions. It does not require an acidic environment for activation, has long-term stability at the site of action, and has satisfactory safety and tolerability. Thus, vonoprazan may address the unmet medical need for the treatment of acid-related diseases.

BACKGROUND: The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS: The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS: Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS: Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .

Proton pump inhibitors are commonly utilized for the treatment of gastric acid-related diseases, such as gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori infection, and for the prevention of low-dose aspirin or nonsteroidal anti-inflammatory drug-induced peptic ulcers. Vonoprazan is a first-in-class potassium-competitive acid blocker, which has distinct advantages compared to other conventional proton pump inhibitors in terms of the efficacy for acid suppression. Due to its strong gastric acid suppression capabilities, vonoprazan serves as an effective drug for the treatment of gastroesophageal reflux disease and H. pylori infection.

Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations (fu x C2) in the stomach were simulated and linked to the antisecretory effects of the drug (I) (increases in pH or acid output) using the fomula dI/dt = k x fu x C2 x (Imax - I) - kd x I. The vonoprazan dissociation rate constant kd (0.00246 min(-1)) and inhibition index KI (35 nM) for H(+)/K(+)-ATPase were obtained from literatures. The vonoprazan-H(+)/K(+)-ATPase binding rate constant k was 0.07028 min(-1). muM(-1) using ratio of kd to KI. The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration.

BACKGROUND: Despite the effectiveness of antireflux fundoplication for typical gastroesophageal reflux disease, outcomes regarding surgical therapy for patients with gastroesophageal reflux disease-related chronic cough are currently unclear. The purpose of this study was to evaluate whether antireflux surgery for patients with chronic cough is effective, and to assess the correlation between indexes, such as symptom index and symptom association probability, and response to surgery. METHODS: We performed a retrospective review of a prospectively collected database from a 3-site institution from 2013 to 2017. Of 1149 patients who underwent antireflux surgery, 41 presented with chronic cough as a main symptom related to gastroesophageal reflux disease. Preoperatively, patients underwent a symptom assessment, esophagogastroduodenoscopy, esophageal 24-h pH monitoring, and manometry. Patients were followed up at 6 weeks and 12 months post-surgery. RESULTS: Thirty-three (80.5%) patients underwent Nissen fundoplication, while 8 (19.5%) underwent Toupet fundoplication. Isolated chronic cough was present in 8 (19.5%) patients, and median (range) DeMeester score was 28.9 (0.3-96.7). After 12-month follow-up, chronic cough was absent in 28 (68.3%) patients (P = .02). Typical reflux symptoms responded well to surgery, but response was not optimal. Postoperative dysphagia and atypical reflux symptoms were slightly worse on long-term follow-up; however, differences were not significant (P >/= .2). When examining how the different symptom indexes correlated with complete, partial, or no response in patients with gastroesophageal reflux disease-related cough, there was no notable agreement on predicted response to surgery. CONCLUSIONS: Antireflux surgery, although less predictable, is effective for the treatment of gastroesophageal reflux disease-related chronic cough.

OBJECTIVE: Although a large body of information exists about the prevalence of gastroesophageal reflux disease (GERD) in general, available data specifically addressing nocturnal reflux are limited. Because nocturnal acid reflux is reported to be associated with more severe injuries such as esophagitis and stricture, as well as adenocarcinoma of the esophagus, a better understanding of the prevalence and impact of nighttime heartburn as a sign of nocturnal acid reflux events can have significant potential management implications. The aims of this study were to determine the prevalence of nighttime heartburn and reflux-attributed supraesophageal symptoms among patients with GERD; and the impact of nighttime heartburn on sleep and several activities of daily living that could affect quality of life. METHODS: A nationwide telephone survey of 1000 adults experiencing heartburn at least once a week was conducted by the Gallup Organization on behalf of the American Gastroenterological Association. RESULTS: Altogether, 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, but only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines, and 49% of these rated this approach extremely effective. CONCLUSIONS: Nighttime heartburn occurs in a large majority of adults with GERD, resulting in sleeping difficulties and impaired next-day function. The expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients.

BACKGROUND: Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. AIM: To verify the non-inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy. METHODS: In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A-D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks. RESULTS: Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non-inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long-term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well-tolerated. CONCLUSIONS: The non-inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well-tolerated and effective during the long-term maintenance study.

OBJECTIVE: The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan. METHODS: This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms. RESULTS: These 55 patients with symptomatic GERD had non-erosive reflux disease (n = 30) or erosive esophagitis (n = 25). Vonoprazan (10 mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%. CONCLUSION: One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.

BACKGROUND: The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders. AIM: To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO). METHODS: In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients >/=20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4. RESULTS: A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups. CONCLUSIONS: Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO.

OBJECTIVE: The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. DESIGN: A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. RESULTS: Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. CONCLUSION: Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. TRIAL REGISTRATION NUMBER: NCT01505127.

BACKGROUND/AIMS: Phase III study demonstrated that vonoprazan-based Helicobacter pylori eradication therapy achieved higher eradication rate compared with lansoprazole. However, there is no study that evaluated the efficacy of vonoprazan in a large sample in real world. We investigated the eradication rate and safety of vonoprazan-based eradication therapy compared with our randomized control trial using second-generation proton pump inhibitor (PPIs). METHODS: (First study) A total of 147 patients who have H. pylori infection were randomly assigned to receive either, esomeprazole (EPZ) group and rabeprazole (RPZ) group. (Second study) 1,688 patients who have H. pylori infection underwent primary eradication with triple therapy involving vonoprazan. In both studies, triple therapy with amoxicillin, clarithromycin, and PPI or vonoprazan was performed, and eradication effect was assessed by an urea breath test. RESULTS: (First study) Eradication rate was 77.5% in the EPZ group and 68.4% in the RPZ group; no significant difference was observed between the 2 groups. (Second study) The successful primary eradication rate was 90.8%. There was no severe adverse effect. CONCLUSIONS: The eradication rate of vonoprazan-based triple therapy was remarkably higher compared with second-generation PPIs-based triple therapy in real world. Vonoprazan is very likely to become the first option for future eradication therapy.

The effects of patient age on the efficacy of eradication treatment for Helicobacter pylori (H. pylori) remain unclear. The present study aimed to determine whether age affects eradication therapy involving vonoprazan, a novel potassium-competitive acid blocker (PCAB). We reviewed the cases of 3,261 patients who were administered first-line and second-line H. pylori eradication therapy at Toyoshima Endoscopy Clinic. The first-line treatment was clarithromycin and amoxicillin combined with a proton pump inhibitor (PPI) or a PCAB. The second-line treatment was metronidazole and amoxicillin combined with a PPI or PCAB. The patients were divided into a young to middle-aged group (age 50 years) as well as into PPI and PCAB groups. The PPI-clarithromycin-amoxicillin regimen demonstrated a significantly lower H. pylori eradication rate than the PCAB-clarithromycin-amoxicillin regimen (p<0.001). With the PPI-clarithromycin-amoxicillin regimen, the eradication rate in the young to middle-aged group was significantly lower than that in the older group (p<0.001). Lastly, age had no impact on the eradication rate of PCAB-based therapy or metronidazole-based therapy. In conclusion, with clarithromycin-based triple therapy, PCAB is a better choice of antisecretory agent compared to PPIs, especially in young to middle-aged patients.

INTRODUCTION: According to the present knowledge, the effect of non-steroidal anti-inflammatory drugs (NSAIDs) depends on the inhibitory ratio of cyclooxigenase (COX)-1 to COX-2 in the plasma membranes. In addition to cardiovascular and gastrointestinal side effects, there are adverse symptoms which can be divided into cross-intolerance (non-immune mediated) and single or multiple hypersensitive (immune mediated) reactions. Due to clinical phenotypes and to in vivo aspirin reactivity, adverse effects could be further classified. AIM: The aim of these studies was a comparison of hit ratios obtained by a humoral serum test measuring specific immunglobulin E (IgE) against a rapid cellular test measuring interleukin (IL)-6 release from sensitized mononuclear cells due to various suspect NSAID after symptoms within one year. Retrospective case studies were performed in in- and out-patients of our teaching hospital in Budapest, between 2003 and 2013. METHOD: Specific anti-NSAID IgE levels were determined by ELISA in 55 cases. The other matching group of patients consisted of 51 patients and 9 tolerant persons. Their separated cells' supernatants were checked for IL-6 release incubated for 20 minutes by NSAID dilutions including intraassay controls by two-step ELISA assay. Both groups have been stratified according to

OBJECTIVE: To determine how often patients with musculoskeletal (MSK) complaints prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult their general practitioner (GP) with a non-serious adverse drug reaction (ADR). DESIGN: Cohort study. SETTING: A healthcare database containing the electronic GP medical records of over 1.5 million patients throughout the Netherlands. PATIENTS: A total of 16 626 adult patients with MSK complaints prescribed an NSAID. MAIN OUTCOME MEASURES: The patients' medical records were manually assessed for the duration of NSAID use for a maximum of two months, and consultations for complaints predefined as potential ADRs were identified. Subsequently, the likelihood of an association with the NSAID use was assessed and these potential ADRs were categorized as likely, possible, or unlikely ADRs. RESULTS: In total, 961 patients (6%) consulted their GP with 1227 non-serious potential ADRs. In 174 patients (1%) at least one of these was categorized as a likely ADR, and in a further 408 patients (2.5%) at least one was categorized as a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). CONCLUSION: Of the patients with MSK complaints prescribed an NSAID, almost one in 30 patients re-consulted their GP with a complaint likely or possibly associated with the use of this drug. The burden of such consultations for non-serious ADRs should be taken into account by GPs when deciding whether treatment with an NSAID is appropriate.

BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases. AIM: To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). METHODS: Patients aged >/=20 years with >/=1 endoscopically-confirmed GU or DU (>/=5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU. RESULTS: For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups. CONCLUSIONS: Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

OBJECTIVE: Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study. DESIGN: Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and [本文引用:1]

OBJECTIVE: Artificial ulcers after endoscopic submucosal dissection (ESD) are usually treated by proton pump inhibitors (PPIs) in clinical setting. Vonoprazan, a newly developed potassium-competitive acid blocker, has recently been used to treat post-ESD ulcers. We aimed to evaluate the efficacy and safety of vonoprazan on the healing of post-ESD artificial ulcers compared with those of proton pump inhibitors (PPIs) using a meta-analysis. METHODS: EMBASE, MEDLINE, Scopus and Cochrane Library databases were searched for all studies comparing the efficacy and safety of vonoprazan with those of PPIs in the treatment of post-ESD ulcers. RESULTS: Fourteen articles with 1328 patients were included in this meta-analysis. When comparing ulcer shrinkage rate, vonoprazan showed a better efficacy than PPIs (mean difference 0.56, 95% confidence interval [CI] 0.18-0.93). Vonoprazan also led to a higher scar formation rate (odds ratio [OR] 1.58, 95% CI 1.00-2.47) and showed a potential superiority on reducing the risk of post-ESD bleeding compared with PPIs, with a pooled OR of 0.69, although there was no statistically significant difference. CONCLUSIONS: Compared with PPIs, vonoprazan showed a better efficacy in ulcer shrinkage rate and achieved more complete healing in the treatment of post-ESD ulcers. Vonoprazan did not induce any incremental risk of post-ESD bleeding as well. It may be an appropriate choice in the management of artificial ulcers after ESD.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole. METHODS: We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD. RESULTS: Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; p = 0.07). However, for ulcers [本文引用:1]

Background: The safety and effectiveness of vonoprazan-based Helicobacter pylori (H. pylori) eradication therapy in routine clinical practice, and patient characteristics that influence safety and effectiveness, have not been well investigated.Methods: H. pylori-positive patients with gastric ulcer, duodenal ulcer, idiopathic thrombocytopenic purpura, history of endoscopic treatment of early gastric cancer, and gastritis were enrolled. Patients received vonoprazan 20 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200-400 mg twice daily for 7 days for the first-line eradication. For the second-line eradication, vonoprazan, AMPC, and metronidazole (MTZ) 250 mg were administered. The incidence of adverse drug reactions (ADRs) and eradication rates were evaluated.Results: The incidences of ADRs with vonoprazan/AMPC/CAM and vonoprazan/AMPC/MTZ were 3.22% (16/497) and 1.89% (1/53), respectively. Commonly reported ADRs were diarrhea, nausea, dysgeusia, feces soft, and rash. The eradication rates of the first-line therapy and the second-line therapy were 91.24% (427/468) and 95.45% (42/44), respectively. No notable differences in ADRs and eradication rates were observed when stratified by patient demographic characteristics.Conclusion: No new safety concerns were observed, and the effectiveness of vonoprazan-based triple therapy was confirmed in routine clinical practice.Trial registration: This study is registered at the Japan Pharmaceutical Information Center Clinical Trials Information (JapicCTI-153003).

BACKGROUND AND AIM: Vonoprazan (VPZ) is a new oral potassium-competitive acid blocker that has recently become available. The aim of this study was to investigate the effects of VPZ on the urease activity of H. pylori as measured by the (13)C-urea breath test ((13)C-UBT). PATIENTS AND METHODS: A total of 60 patients (26 men, 34 women; mean age 53.2 +/- 13.6 years) who were diagnosed as H. pylori-positive were recruited. The patients were randomly allocated to three treatment groups: lansoprazole (LPZ) 30 mg (n = 20), VPZ 20 mg (n = 20) once daily for 3 weeks, or the control group (n = 20). The (13)C-UBT was carried out at baseline and after 3 weeks of treatment, and the baseline and after treatment results then compared. Delta(13)C per thousand >/= 2.5 per thousand was considered H. pylori-positive. RESULTS: Four patients failed to complete the medication and were omitted from the analysis; data from the LPZ group (n = 18), VPZ group (n = 18), and control group (n = 20) were analyzed. The control group showed no significant change in (13)C-UBT data between baseline and the completion of 3-week treatment (baseline: 26.6 +/- 23.0 per thousand, completion: 21.1 +/- 13.1 per thousand). The (13)C-UBT data at week 3 were significantly decreased in both the VPZ group (baseline: 32.8 +/- 22.7 per thousand, completion: 7.6 +/- 9.2 per thousand, p = 0.0002) and the LPZ group (baseline: 41.8 +/- 33.4 per thousand; completion: 9.6 +/- 8.8 per thousand, p = 0.0006) compared to baseline. CONCLUSIONS: VPZ treatment reduced the value of UBT, warning that UBT for patients with VPZ treatment should be evaluated carefully.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is expected to improve the healing of endoscopic submucosal dissection (ESD)-induced gastric ulcers compared with proton pump inhibitors (PPIs). AIM: To compare the healing status of ESD-induced gastric ulcers and the incidence of post-ESD bleeding between subjects treated with vonoprazan for 5 weeks and those treated with PPIs for 8 weeks. METHODS: Patients in the vonoprazan group (n = 75) were prospectively enrolled, whereas patients in the PPI group (n = 150) were selected for a 2:1 matched historical control cohort according to baseline characteristics including gastric ulcer size immediately following ESD, age, sex and status of Helicobacter pylori infection. Two controls per case of vonoprazan-treated group were matched with a margin of 20% in terms of ulcer size and a margin of 5 years in terms of their age. RESULTS: Although a higher number of completely healed ulcers was observed in the PPI group (95/150, 63.3%) than that in the vonoprazan group (14/75, 18.7%; P < 0.001), the ulcer size reduction rates, which were 96.0 +/- 6.7% in the vonoprazan group and 94.7 +/- 11.6% in the PPI group, were not significantly different (P = 0.373). The post-ESD bleeding incidence in the vonoprazan group (1/75, 1.3%) was less than that in the PPI group (15/150, 10.0%; P = 0.01). The factors affecting post-ESD bleeding incidence were the type of acid secretion inhibitor (P = 0.016) and use of an anti-thrombotic agent (P = 0.014). CONCLUSION: Vonoprazan significantly reduced post-endoscopic submucosal dissection bleeding compared with PPIs.

Vonoprazan fumarate (Takecab) is a first-in-class potassium-competitive acid blocker that has been available in the market in Japan since February 2015. Vonoprazan is administered orally at 20 mg once daily for the treatment of gastroduodenal ulcer, at 20 and 10 mg once daily for the treatment and secondary prevention of reflux esophagitis, respectively, at 10 mg once daily for the secondary prevention of low-dose aspirin- or non-steroidal anti-inflammatory drug-induced peptic ulcer, and at 20 mg twice daily in combination with clarithromycin and amoxicillin for the eradication of Helicobacter pylori. It inhibits H(+),K(+)-ATPase activities in a reversible and potassium-competitive manner with a potency of inhibition approximately 350 times higher than the proton pump inhibitor, lansoprazole. Vonoprazan is absorbed rapidly and reaches maximum plasma concentration at 1.5-2.0 h after oral administration. Food has minimal effect on its intestinal absorption. Oral bioavailability in humans remains unknown. The plasma protein binding of vonoprazan is 80% in healthy subjects. It distributes extensively into tissues with a mean apparent volume of distribution of 1050 L. Being a base with pKa of 9.6 and with acid-resistant properties, vonoprazan is highly concentrated in the acidic canaliculi of the gastric parietal cells and elicited an acid suppression effect for longer than 24 h after the administration of 20 mg. The mean apparent terminal half-life of the drug is approximately 7.7 h in healthy adults. Vonoprazan is metabolized to inactive metabolites mainly by cytochrome P450 (CYP)3A4 and to some extent by CYP2B6, CYP2C19, CYP2D6, and SULT2A1. A mass balance study showed that 59 and 8% of the orally administered radioactivity was recovered in urine as metabolites and in an unchanged form, respectively, indicating extensive metabolism. Genetic polymorphism of CYP2C19 may influence drug exposure but only to a clinically insignificant extent (15-29%), according to the population pharmacokinetic study performed in Japanese patients. When vonoprazan was co-administered with clarithromycin, the mean AUC from time 0 to time of the next dose (dosing interval) of vonoprazan and clarithromycin were increased by 1.8 and 1.5 times, respectively, compared with the corresponding control values, indicating mutual metabolic inhibition. The mean area under the curve from time zero to infinity obtained from patients with severe liver and renal dysfunction were elevated by 2.6 and 2.4 times, respectively, compared with healthy subjects, with no significant changes in plasma protein binding. Vonoprazan increases intragastric pH above 4.0 as early as 4 h after an oral dose of 20 mg, and the extensive anti-secretory effect is maintained up to 24 h post-dose. During repeated dosing of 20 mg once daily, the 24-h intragastric pH >4 holding time ratios were 63 and 83 % on days 1 and 7, respectively. Because vonoprazan elicited a more extensive gastric acid suppression than the proton pump inhibitor, lansoprazole, it also gave rise to two to three times greater serum gastrin concentrations as compared with lansoprazole. In pre-approval clinical studies for the treatment of acid-related disorders, mild to moderate adverse drug reactions (mostly constipation or diarrhea) occurred at frequencies of 8-17%. Neither severe liver toxicity nor neuroendocrine tumor has been reported in patients receiving vonoprazan.