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强效钾离子竞争性酸阻滞剂:治疗酸相关性疾病的新时代。

Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases.

作者信息

Oshima Tadayuki, Miwa Hiroto

机构信息

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

出版信息

J Neurogastroenterol Motil. 2018 Jul 30;24(3):334-344. doi: 10.5056/jnm18029.


DOI:10.5056/jnm18029
PMID:29739175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6034668/
Abstract

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.

摘要

传统质子泵抑制剂(PPIs)在全球范围内被用作治疗酸相关性疾病的一线疗法。然而,它们存在一些局限性,包括起效缓慢、受细胞色素P450基因多态性影响、夜间效果不理想以及在酸性条件下不稳定。为克服这些问题,已开发出传统PPIs的替代剂型;然而,与传统PPIs相比,这些药物在控制胃酸分泌方面仅带来了微小优势。钾竞争性酸阻滞剂(P-CABs)被研发出来,具有包括快速、持久且可逆地抑制胃氢钾ATP酶(胃质子泵)等有益作用。沃克最近被创新为一种新型的口服活性P-CAB。在日本,它目前被用于治疗胃溃疡和十二指肠溃疡、反流性食管炎,以及预防低剂量阿司匹林或非甾体抗炎药相关的胃溃疡和十二指肠溃疡复发。沃克由于酸稳定不需要肠溶包衣,并且因为吸收迅速可以空腹服用。沃克在酸性和中性条件下均会在壁细胞中蓄积。它不需要酸性环境来激活,在作用部位具有长期稳定性,并且具有令人满意的安全性和耐受性。因此,沃克可能满足酸相关性疾病治疗中未被满足的医疗需求。

相似文献

[1]
Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases.

J Neurogastroenterol Motil. 2018-7-30

[2]
Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438).

Adv Ther. 2016-7

[3]
Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases.

Pharmacol Ther. 2016-8-8

[4]
The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations.

Clin Pharmacokinet. 2016-4

[5]
The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+ -ATPase.

Aliment Pharmacol Ther. 2015-12

[6]
Vonoprazan Fumarate for the Treatment of Gastric Ulcers: A Short Review on Emerging Data.

Clin Exp Gastroenterol. 2020-4-15

[7]
Vonoprazan fumarate for the management of acid-related diseases.

Expert Opin Pharmacother. 2017-8

[8]
[Pharmacological characteristics and clinical efficacies of a novel potassium-competitive acid blocker, vonoprazan fumarate].

Nihon Yakurigaku Zasshi. 2018

[9]
[Treatment of Acid-related Diseases Using Potassium-competitive Acid Blockers].

Korean J Gastroenterol. 2022-12-25

[10]
Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date.

Therap Adv Gastroenterol. 2018-1-9

引用本文的文献

[1]
Tegoprazan dual and quadruple therapy for eradication: a prospective, randomized controlled trial in Beijing, China.

Front Med (Lausanne). 2025-8-12

[2]
Research progress of potassium-competitive acid blockers in the treatment of .

Ann Med. 2025-12

[3]
Follow-up study of vonoprazan maintenance therapy for reflux esophagitis: A 96-week evaluation in patients with PPI-refractory disease.

Biomed Rep. 2025-7-30

[4]
Drug treatment strategies for erosive esophagitis in adults: a narrative review.

Transl Gastroenterol Hepatol. 2025-7-23

[5]
Prescription trends of gastric acid suppressants and association with potential adverse events in Korea: a real-world cross-sectional study.

Therap Adv Gastroenterol. 2025-7-15

[6]
Long-term Effects of Potassium-competitive Acid Blockers and Proton Pump Inhibitors on Gastrin, Gastric Emptying Rate, and Small Intestinal Microbiota in Rats.

J Neurogastroenterol Motil. 2025-7-30

[7]
Effect of Tegoprazan on Tacrolimus and Mycophenolate Levels in Kidney Transplant Recipients: A Randomized Controlled Study Using a Smart Trial Platform.

Pharmaceuticals (Basel). 2025-6-1

[8]
Comparing Proton Pump Inhibitors and Emerging Acid-Suppressive Therapies in Gastroesophageal Reflux Disease: A Systematic Review.

Cureus. 2025-5-17

[9]
[History and Pharmacological Mechanism of Gastric Acid-suppressive Drugs].

Korean J Helicobacter Up Gastrointest Res. 2023-9

[10]
[Potassium-competitive Acid Blockers: A New Therapeutic Strategy for Eradication].

Korean J Helicobacter Up Gastrointest Res. 2023-9

本文引用的文献

[1]
Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date.

Therap Adv Gastroenterol. 2018-1-9

[2]
Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial.

Helicobacter. 2017-12-21

[3]
Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study.

Gut. 2017-12-1

[4]
Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

J Pharmacol Exp Ther. 2017-11-27

[5]
Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study.

Gut. 2017-10-7

[6]
Antibiotic susceptibility, heteroresistance, and updated treatment strategies in infection.

Drug Des Devel Ther. 2017-7-28

[7]
Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth.

J Gastroenterol. 2017-8-2

[8]
Magnitude and direction of the association between Clostridium difficile infection and proton pump inhibitors in adults and pediatric patients: a systematic review and meta-analysis.

J Gastroenterol. 2017-7-25

[9]
KFP-H008 blocks gastric acid secretion through inhibiting H-K-ATPase.

Eur J Pharmacol. 2017-6-16

[10]
Effects of patient age and choice of antisecretory agent on success of eradication therapy for infection.

J Clin Biochem Nutr. 2017-5

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