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作为一种新型镇咳治疗药物,gefapixant 的发现和开发。

The discovery and development of gefapixant as a novel antitussive therapy.

机构信息

Unit of Pharmacology, Department of Experimental Medicine, School of Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Unit of Respiratory Medicine, Department Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

出版信息

Expert Opin Drug Discov. 2024 Oct;19(10):1159-1172. doi: 10.1080/17460441.2024.2391902. Epub 2024 Aug 13.

Abstract

INTRODUCTION

Gefapixant, a P2X 3 receptor antagonist, shows considerable potential in managing refractory or unexplained chronic cough. Clinical trials have consistently demonstrated its efficacy in significantly reducing cough frequency and alleviating associated symptoms. However, its adverse effect profile, particularly taste disturbances such as dysgeusia and hypogeusia, the incidence of which is dose-dependent, poses a significant challenge to patient compliance and overall treatment satisfaction.

AREAS COVERED

The authors review the mechanism of action of gefapixant, the dose-dependent nature of its adverse effects and the findings from various clinical trials, including Phase 1, Phase 2, and Phase 3 studies. The authors also cover its regulatory status, post-marketing data, and its main competitors.

EXPERT OPINION

Gefapixant represents a significant advancement in treating chronic cough. However, balancing efficacy and tolerability is crucial. Lower effective doses and potential combination therapies may mitigate taste disturbances. Patient education and close monitoring during treatment are also important for optimal outcomes. Further research is needed to refine dosing strategies to minimize side effects while maintaining therapeutic efficacy. This research and personalized treatment approaches are key to optimizing gefapixant therapy, ensuring improved management of chronic cough while reducing adverse effects. However, pharmaceutical trials and proposals must be adapted to align with each regulatory body's specific requirements and concerns.

摘要

简介

Gefapixant 是一种 P2X3 受体拮抗剂,在治疗难治性或原因不明的慢性咳嗽方面具有很大的潜力。临床试验一致表明,它能显著降低咳嗽频率并缓解相关症状。然而,其不良效应谱,尤其是味觉障碍(如味觉异常和味觉减退),其发生率与剂量有关,这对患者的依从性和整体治疗满意度构成了重大挑战。

涵盖领域

作者回顾了 gefapixant 的作用机制、其不良反应的剂量依赖性以及来自各种临床试验的发现,包括 1 期、2 期和 3 期研究。作者还涵盖了其监管状况、上市后数据以及其主要竞争对手。

专家意见

Gefapixant 代表了治疗慢性咳嗽的重大进展。然而,平衡疗效和耐受性至关重要。较低的有效剂量和潜在的联合治疗可能会减轻味觉障碍。在治疗过程中对患者进行教育和密切监测对于获得最佳结果也很重要。需要进一步研究来完善剂量策略,以尽量减少副作用,同时保持治疗效果。这种研究和个性化治疗方法是优化 gefapixant 治疗的关键,确保在减少不良反应的同时改善慢性咳嗽的管理。然而,药物试验和提案必须适应每个监管机构的具体要求和关注。

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