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新型钾离子竞争性酸阻滞剂富马酸沃克索拉唑(TAK-438)的特性

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

作者信息

Otake Kazuyoshi, Sakurai Yuuichi, Nishida Haruyuki, Fukui Hideo, Tagawa Yoshihiko, Yamasaki Hitomi, Karashima Masatoshi, Otsuka Keiichi, Inatomi Nobuhiro

机构信息

Global Medical Affairs Japan Department, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan.

Clinical Science, Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.

出版信息

Adv Ther. 2016 Jul;33(7):1140-57. doi: 10.1007/s12325-016-0345-2. Epub 2016 Jun 10.


DOI:10.1007/s12325-016-0345-2
PMID:27287852
Abstract

UNLABELLED: Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux disease, and for the eradication of Helicobacter pylori. However, the therapeutic efficacy of conventional PPIs is considered limited because: (1) they are unstable under acidic conditions and require an enteric-coated formulation in clinical use; (2) they show high interindividual variability in pharmacokinetics due to genetic polymorphisms of cytochrome P450 (CYP) 2C19 metabolism; (3) they have a relatively slow onset of pharmacological action and may require several doses to achieve optimal acid suppression and symptom relief; and (4) they often do not provide stable suppression of gastric acid secretion over 24 h. Vonoprazan fumarate (TAK-438, hereinafter referred to as "vonoprazan") is a new potassium-competitive acid blocker (P-CAB) developed to resolve the above limitations of conventional PPIs. Various physicochemical data have shown that vonoprazan has a high solubility and stability over a broad pH range in aqueous conditions. In addition, vonoprazan has a more potent and longer-lasting acid suppression effect than the conventional PPI, lansoprazole. Preclinical pharmacokinetic studies have shown that vonoprazan is accumulated and retained in the stomach for more than 24 h, even after it is eliminated from the plasma. From these findings, we propose that vonoprazan, which possesses a novel mode of action, can improve on the outcomes seen with conventional PPI-based treatments for acid-related diseases. FUNDING: This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.

摘要

未标注:质子泵抑制剂(PPIs)被广泛用作治疗酸相关疾病(如消化性溃疡和胃食管反流病)以及根除幽门螺杆菌的一线疗法。然而,传统质子泵抑制剂的治疗效果被认为是有限的,原因如下:(1)它们在酸性条件下不稳定,临床使用时需要肠溶包衣制剂;(2)由于细胞色素P450(CYP)2C19代谢的基因多态性,它们在药代动力学上表现出较高的个体间变异性;(3)它们的药理作用起效相对较慢,可能需要多次给药才能达到最佳的胃酸抑制和症状缓解效果;(4)它们通常无法在24小时内持续稳定地抑制胃酸分泌。富马酸沃克帕唑(TAK-438,以下简称“沃克帕唑”)是一种新开发的钾竞争性酸阻滞剂(P-CAB),旨在解决传统质子泵抑制剂的上述局限性。各种理化数据表明,沃克帕唑在水性条件下的广泛pH范围内具有高溶解度和稳定性。此外,沃克帕唑比传统质子泵抑制剂兰索拉唑具有更强、更持久的胃酸抑制作用。临床前药代动力学研究表明,即使沃克帕唑从血浆中消除后,它仍会在胃中蓄积并保留超过24小时。基于这些发现,我们提出,具有新型作用模式的沃克帕唑可以改善基于传统质子泵抑制剂治疗酸相关疾病的效果。 资助:本综述项目,包括本文的发表,由武田制药有限公司资助。

相似文献

[1]
Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438).

Adv Ther. 2016-7

[2]
Vonoprazan fumarate for the management of acid-related diseases.

Expert Opin Pharmacother. 2017-8

[3]
The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations.

Clin Pharmacokinet. 2016-4

[4]
The Effects of Switching to Vonoprazan, a Novel Potassium-Competitive Acid Blocker, on Gastric Acidity and Reflux Patterns in Patients with Erosive Esophagitis Refractory to Proton Pump Inhibitors.

Digestion. 2017

[5]
[Pharmacological characteristics and clinical efficacies of a novel potassium-competitive acid blocker, vonoprazan fumarate].

Nihon Yakurigaku Zasshi. 2018

[6]
A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals.

J Pharmacol Exp Ther. 2011-3-16

[7]
Vonoprazan: A Novel and Potent Alternative in the Treatment of Acid-Related Diseases.

Dig Dis Sci. 2017-12-27

[8]
Vonoprazan versus conventional proton pump inhibitor-based triple therapy as first-line treatment against Helicobacter pylori: A multicenter retrospective study in clinical practice.

J Dig Dis. 2016-10

[9]
Vonoprazan, a Novel Potassium-Competitive Acid Blocker, Should Be Used for the Helicobacter pylori Eradication Therapy as First Choice: A Large Sample Study of Vonoprazan in Real World Compared with Our Randomized Control Trial Using Second-Generation Proton Pump Inhibitors for Helicobacter pylori Eradication Therapy.

Digestion. 2018-1-31

[10]
1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases.

J Pharmacol Exp Ther. 2010-7-12

引用本文的文献

[1]
Vonoprazan-minocycline dual therapy as a first-line treatment of infection compared with empirical bismuth-containing quadruple therapy.

Therap Adv Gastroenterol. 2025-8-22

[2]
Vonoprazan-associated Microscopic Colitis and Continued Use After Onset: A Study Using a Japanese Pharmacovigilance Database.

In Vivo. 2025

[3]
Current research status and trends of potassium-competitive acid blockers in the treatment of acid-related diseases: a bibliometric analysis.

Front Pharmacol. 2025-1-7

[4]
The efficacy and safety of a simple 14-day vonoprazan-minocycline dual therapy for eradication: a retrospective pilot study.

Therap Adv Gastroenterol. 2024-11-19

[5]
Vonoprazan-Associated Mucosal Redness: A Report of Two Cases.

Cureus. 2024-10-12

[6]
Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments.

Curr Gastroenterol Rep. 2024-11

[7]
Vonoprazan a novel potassium competitive acid blocker; another leap forward.

Prz Gastroenterol. 2024

[8]
P-CAB PPI in the eradication of : a systematic review and network meta-analysis.

Therap Adv Gastroenterol. 2024-5-14

[9]
Deep learning driven de novo drug design based on gastric proton pump structures.

Commun Biol. 2023-9-19

[10]
Efficacy and safety of vonoprazan-amoxicillin dual therapy for first-line treatment: a single-center, randomized, controlled trial.

Therap Adv Gastroenterol. 2023-8-30

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