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钾离子竞争型酸阻断剂:当前临床应用与未来发展。

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

机构信息

Department of Medicine & Surgery, University of Parma, Parma, Italy.

Department of Health Sciences, United Campus of Malta, Msida, Malta.

出版信息

Curr Gastroenterol Rep. 2024 Nov;26(11):273-293. doi: 10.1007/s11894-024-00939-3. Epub 2024 Aug 15.

Abstract

PURPOSE OF THE REVIEW

Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice.

RECENT FINDINGS

Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

摘要

目的综述

质子泵抑制剂 (PPI) 的抑酸作用代表了酸相关疾病治疗的标准。然而,尽管它们有效,但 PPI 存在一些内在的局限性,这是过去几十年中发现的未满足的临床需求的基础。本综述的目的是总结最近引入医学实践的新型抗分泌药物(钾竞争酸阻滞剂,P-CAB)的现状和未来发展。

最新发现

在过去的几十年中,人们认识到当前酸抑制剂未满足的临床需求,特别是在胃食管反流病 (GERD)、幽门螺杆菌感染和 NSAID 相关消化性溃疡的治疗中。未能满足这些需求主要是由于它们无法在所有患者中实现一致的抑酸作用,特别是无法控制夜间酸度。然后人们意识到延长抑酸时间将产生额外的益处。目前可用的 P-CAB 数据表明,它们能够满足这些未满足的临床需求。目前有四种不同的 P-CAB(沃诺拉赞、替戈拉赞、非索拉赞和凯维拉唑)。然而,只有两种在亚洲以外获得批准。沃诺拉赞可在北美、中美和南美使用,而替戈拉赞仅在拉丁美洲国家销售。另外两种化合物(即林扎普拉赞葡萄糖酸盐和泽替拉唑)目前正在临床开发中。虽然所有 P-CAB 都已进行了 GERD 的临床试验,但只有沃诺拉赞和替戈拉赞被研究作为幽门螺杆菌根除方案的组成部分。现有数据表明,在上述两种临床适应症中,P-CAB 与 PPI 相比提供相似或更好的疗效。它们在短期的安全性与 PPI 重叠,但需要长期治疗的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb8/11401795/b9aeefa4177b/11894_2024_939_Fig1_HTML.jpg

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