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静脉注射司来帕格在治疗肺动脉高压及弥补口服治疗差距中的作用:一项叙述性综述

The Role of Intravenous Selexipag in Managing PAH and Bridging Gaps in Oral Treatment: A Narrative Review.

作者信息

Goren Sienna, Kidwai Nermeen, Aronow Wilbert S, Lanier Gregg M

机构信息

New York Medical College, Valhalla, NY, USA.

Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA.

出版信息

Ther Clin Risk Manag. 2025 Jan 10;21:55-60. doi: 10.2147/TCRM.S332358. eCollection 2025.

Abstract

Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure. To address treatment interruptions, intravenous (IV) selexipag was introduced as an alternative for patients who are temporarily unable to take oral medications. IV selexipag bypasses hepatic metabolism, requiring a 12.5% higher dose compared to the oral form to achieve similar therapeutic effects. It is administered via IV infusion twice daily over 80 minutes, typically for short-term use. However, caution is needed when prescribing selexipag to patients with hepatic or renal issues, and it is contraindicated with strong CYP2C8 inhibitors. A Phase III clinical trial confirmed that switching between oral and IV selexipag was safe, with comparable efficacy and tolerability, though it was limited by small sample size and short duration. Given the risks of treatment interruption and the complexity of managing PAH, this review provides essential insights into the practical use of IV selexipag as a bridging therapy. Furthermore, it calls for larger clinical trials to refine dosing strategies, explore long-term outcomes, and identify patient populations most likely to benefit from IV selexipag.

摘要

肺动脉高压(PAH)是一种罕见且可能致命的疾病,其特征是肺血管动脉血压逐渐升高。口服司来帕格于2015年获得美国食品药品监督管理局(FDA)批准用于治疗PAH,它作用于肺动脉血管平滑肌和内皮细胞上的前列环素受体,以改善肺部血流并降低肺血管阻力。口服司来帕格是有效的,但可能因副作用、紧急情况或无法口服药物等因素而停药,这可能导致严重不良事件,如反弹性肺动脉高压和右心衰竭。为解决治疗中断问题,引入了静脉注射(IV)司来帕格,作为暂时无法口服药物的患者的替代治疗方法。静脉注射司来帕格绕过肝脏代谢,与口服剂型相比,需要高12.5%的剂量才能达到相似的治疗效果。它通过静脉输注给药,每天两次,每次80分钟,通常用于短期使用。然而,给有肝脏或肾脏问题的患者开司来帕格时需要谨慎,并且与强效CYP2C8抑制剂禁忌联用。一项III期临床试验证实,在口服和静脉注射司来帕格之间切换是安全的,疗效和耐受性相当,不过该试验受样本量小和持续时间短的限制。鉴于治疗中断的风险以及PAH管理的复杂性,本综述提供了关于静脉注射司来帕格作为桥接治疗实际应用的重要见解。此外,它呼吁进行更大规模的临床试验,以完善给药策略、探索长期结果,并确定最可能从静脉注射司来帕格中获益的患者群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d52d/11733194/026a14a707dd/TCRM-21-55-g0001.jpg

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