Characterization of a Novel Potassium-Competitive Acid Blocker of the Gastric H,K-ATPase, 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1<i>H</i>-pyrrol-3-yl]-<i>N</i>-methylmethanamine Monofumarate (TAK-438)

Shin, Jai Moo; Inatomi, Nobuhiro; Munson, Keith; Strugatsky, David; Tokhtaeva, Elmíra; Vagin, Olga; Sachs, George

doi:10.1124/jpet.111.185314

Cited by 126 publications

(132 citation statements)

References 30 publications

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“…In Japan, 3 kinds of PPI – Esomeprazole, Lansoprazole and Rabeprazole – and a new type of PPI (vonoprazan) were adopted to be covered by health insurance [19, 20]. Recent reports indicated the effectiveness of vonoprazan in patients with reflux esophagitis refractory or resistant to PPIs [21-23].…”

Section: Introductionmentioning

confidence: 99%

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors

Shiotani¹,

Katsumata²,

Gouda³

et al. 2018

Digestion

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Background/Aim: The use of proton pump inhibitors (PPIs) is known to lead to hypergastrinemia; however, the data in patients with atrophic gastritis is still lacking. The aim of this study was to investigate the effects of long-term PPIs use on the gastrin levels in patients with atrophic gastritis and to determine factors affecting hypergastrinemia in long-term users of PPIs. Methods: Serum Helicobacter pylori IgG, gastrin and pepsinogen levels were measured. Atrophic gastritis was assessed by upper gastrointestinal endoscopies based on the Kimura-Takemoto classification and pepsinogen levels. CYP2C19 polymorphisms were assessed using DNA extracted from peripheral blood. Results: A total number of 382 patients (275 men and 107 women) were enrolled. Median serum gastrin levels were higher in PPI users than in non- users (234 vs. 113 pg/mL, p < 0.001) and in women than in men (252 vs. 155 pg/mL, p = 0.006). Gastrin levels were significantly associated with corpus atrophy only in the subgroup of non-users of PPIs. Multivariate analysis revealed that hypergastrinemia (over 150 pg/mL) was significantly associated with PPI use (OR 5.30; 95% CI 3.32–8.47), women (OR 2.22; 95% CI 1.33–3.72) and corpus atrophy (OR 1.82; 95% CI 1.14–2.90). Conclusion: PPI use, women and corpus atrophy were risk factors for hypergastrinemia. Gender, but not corpus atrophy, affected the gastrin levels in long-term users of PPIs.

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Section: Introductionmentioning

confidence: 99%

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors

Shiotani¹,

Katsumata²,

Gouda³

et al. 2018

Digestion

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“…In comparison with PPIs, PCABs bind to the proton pump continuously in gastric parietal cells to reduce gastric acid secretion without requiring activation or being deactivated by the gastric acid. Furthermore, it was reported that PCABs are not affected by genetic polymorphisms of CYP2C19 (23,24). In patients with GERD whose gastric acid secretion was not suppressed sufficiently well by the administration of a PPI, it may be possible to control the secretion further by administering a PCAB.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of a Potassium-Competitive Acid Blocker for Improving Symptoms in Patients with Reflux Esophagitis, Non-Erosive Reflux Disease, and Functional Dyspepsia

et al. 2017

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“…VPZ is a novel oral potassium-competitive acid blocker and is being increasingly used for the treatment of ulcers and reflux esophagitis in Japan (14,15). Compared with LPZ, VPZ exhibits more potent and sustained acid-inhibitory effects, and induction of greater increases in gastric pH, consistent with the observation that VPZ accumulates to higher concentrations and is cleared at a slower rate from gastric glands (16,17).…”

Section: Eradication Rate % (N) -------------------------------------mentioning

confidence: 99%

Second‑line triple therapy in failures with vonoprazan‑based triple therapy for eradication of Helicobacter pylori

et al. 2018

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Abstract. Gastric acid inhibition during treatment is important for the eradication of Helicobacter pylori (H. pylori) infection. A novel potassium-competitive acid blocker, vonoprazan (VPZ), has been demonstrated to achieve high eradication rates; however, the efficacy of second-line treatment in failures of VPZ-based triple therapy has not been well studied.The aim of the current study was to determine the efficacy of VPZ in a first-line regimen for H. pylori eradication, and the efficacy of a second-line regimen using metronidazole (MTZ) in failures with the first-line regimen. Of 580 subjects enrolled in the study, 524 patients completed first-line treatment (275 patients who received VPZ and 249 patients who received LPZ). First-line regimens consisted of a combination of clarithromycin (CAM) 200 or 400 mg twice a day, amoxicillin (AMPC) 750 mg twice a day, and either LPZ 30 mg or VPZ 20 mg twice a day, administered orally for 7 days. CAM and VPZ/LPZ were replaced with metronidazole (MTZ) 250 mg and rabeprazole 10 mg in the second-line regimens. The eradication of H. pylori was assessed by the H. pylori stool antigen test. The overall first-line eradication rate with VPZ was significantly higher than that with LPZ [91.0% (250/275) vs. 84.7% (211/249), respectively, P=0.030]. The dose of CAM (400 vs. 800 mg) did not affect the eradication rate in either the VPZ or LPZ regimens. The overall eradication rates of the second-line regimens with MTZ did not differ significantly between the VPZ-failure and LPZ-failure groups [87.0% (20/23) vs. 87.9% (29/33), respectively, P= 0.700]. Therefore, VPZ was significantly more effective than LPZ for first-line treatment. In patients with failure of first-line eradication therapy, successful results of second-line eradication therapy did not differ between the VPZ-and LPZ-failure groups. In conclusion, VPZ-based triple therapy should be recommended for eradication of H. pylori.

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Characterization of a Novel Potassium-Competitive Acid Blocker of the Gastric H,K-ATPase, 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine Monofumarate (TAK-438)

Cited by 126 publications

References 30 publications

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors

Hypergastrinemia in Long-Term Use of Proton Pump Inhibitors

Efficacy of a Potassium-Competitive Acid Blocker for Improving Symptoms in Patients with Reflux Esophagitis, Non-Erosive Reflux Disease, and Functional Dyspepsia

Second‑line triple therapy in failures with vonoprazan‑based triple therapy for eradication of Helicobacter pylori

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