W1091 Effects of Tak-438, a Novel Potassium-Competitive Acid Blocker (P-Cab), on Gastric Acid Secretion in Animals

Hori, Yasunobu; Matsukawa, Jun; Tsukimi, Yasuhiro; Nishida, Haruyuki; Arikawa, Yasuyoshi; Hirase, Keizo; Imanishi, Akihito; Kajino, Masahiro; Inatomi, Nobuhiro

doi:10.1016/s0016-5085(10)62990-3

Cited by 2 publications

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“…Potassium-competitive acid blockers (P-CABs) are novel acidsuppressing drugs that competitively inhibit the binding of potassium ions to H+/K + -ATPase in gastric parietal cells. Since P-CAB, especially vonoprazan (VPZ), a representative drug of P-CAB, has a relatively high pKa value, does not require acid activation, and is not influenced by CYP2C19 pharmacogenetic polymorphism, it can achieve stronger, longer-lasting gastric acid secretion suppression (Saitoh et al, 2002;Sugimoto et al, 2006;Hori et al, 2010;Scott et al, 2015). Previous study has demonstraded that VPZ produces a stronger acid-inhibitory effect than PPIs (Kiyotoki et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori

Zhang

Liu

et al. 2023

Front. Pharmacol.

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Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism.Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism.Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome.Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05097846

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Section: Introductionmentioning

confidence: 99%

The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori

Zhang

Liu

et al. 2023

Front. Pharmacol.

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“…Vonoprazan has a different mechanism of action and a number of advantages compared with PPIs; it does not require an acidic environment for activation, it is acid stable, and it has been shown to rapidly exert an acid-inhibitory effect (PPIs require 3-5 days for maximal effect). Preclinical studies demonstrated that the acid inhibition achieved by vonoprazan was more potent and longer lasting than that with PPIs [Hori et al 2010[Hori et al , 2011Matsukawa et al 2011]. Importantly, recent clinical trials have also shown vonoprazan to be noninferior to the PPI lansoprazole in terms of EE healing [Ashida et al 2015[Ashida et al , 2016.…”

Section: Introductionmentioning

confidence: 99%

A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis

Iwakiri

Sakurai

Shiino

et al. 2017

Therap Adv Gastroenterol

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Background:Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE.MethodsThis randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint. Following a 7 to 14-day run-in period (lansoprazole 30 mg treatment), patients with endoscopically confirmed PPI-resistant EE received vonoprazan 20 mg or 40 mg for 8 weeks.ResultsPatients were randomized to receive vonoprazan 20 mg (n = 9) or 40 mg (n = 10). Over a 24-hour period; both groups showed a significant increase from baseline in the percentage of time gastric pH ≥ 4, referred to as pH 4 holding time ratio (HTR): an increase from 73.21% to 96.46% in the 20 mg group, and from 69.97% to 100.00% in the 40 mg group. Increases from baseline in esophageal pH 4 HTRs were not significant. The 40 mg group showed greater increases in gastric and esophageal pH 4 HTRs compared with the 20 mg group, but differences between groups were not significant. After 8 weeks’ treatment, the healing rate in subjects with baseline EE grades A–D was 60.0% (3/5 patients) in the 20 mg group and 71.4% (5/7 patients) in the 40 mg group. Vonoprazan was generally well tolerated. One patient (40 mg group) experienced four treatment-emergent adverse events (TEAEs) (unrelated to study drug), leading to study discontinuation.ConclusionsVonoprazan 20 mg and 40 mg effectively inhibited gastric acid secretion over a 24-hour period with significantly increased gastric pH 4 HTR, and resulted in an EE healing rate > 60.0% in this study. Vonoprazan treatment may be valuable for patients with PPI-resistant EE

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W1091 Effects of Tak-438, a Novel Potassium-Competitive Acid Blocker (P-Cab), on Gastric Acid Secretion in Animals

Cited by 2 publications

References 0 publications

The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori

The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori

A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis

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