Greig Sarah L, Scott Lesley J, Plosker Greg L
Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand,
Am J Cardiovasc Drugs. 2014 Dec;14(6):463-70. doi: 10.1007/s40256-014-0093-0.
A bioequivalent formulation of intravenous epoprostenol containing the excipients arginine and sucrose (epoprostenol AS) (Veletri®, Caripul®) is approved in the USA, UK, and other countries for the treatment of pulmonary arterial hypertension (PAH), and has improved thermal stability compared with epoprostenol containing glycine and mannitol (epoprostenol GM) (Flolan®). Epoprostenol, a synthetic prostacyclin, is a potent pulmonary vasodilator. Epoprostenol GM was originally approved for use as a long-term continuous infusion in patients with PAH nearly 20 years ago in the USA; however, this formulation has limited stability at room temperature, and requires the use of cooling or frequent medication changes during administration. The prolonged thermal stability of epoprostenol AS compared with epoprostenol GM allows for its extended administration at room temperature and/or refrigerated storage of prepared solutions. This article summarizes the pharmacology of epoprostenol AS and reviews its therapeutic use in adult patients with PAH. In clinical trials, epoprostenol AS provided sustained efficacy in terms of hemodynamic and symptomatic outcomes, and was generally well tolerated after transitioning from stable epoprostenol GM therapy and during an open-label extension study. Furthermore, there was a significant increase in the treatment convenience with epoprostenol AS compared with epoprostenol GM. Therefore, epoprostenol AS is a valuable therapeutic option that has the potential to overcome some of the limitations of long-term intravenous epoprostenol therapy in patients with PAH.
一种含有辅料精氨酸和蔗糖的静脉注射用依前列醇生物等效制剂(依前列醇AS)(商品名:Veletri®、Caripul®)已在美国、英国和其他国家获批用于治疗肺动脉高压(PAH),与含有甘氨酸和甘露醇的依前列醇(依前列醇GM)(商品名:Flolan®)相比,其热稳定性有所提高。依前列醇是一种合成的前列环素,是一种强效的肺血管扩张剂。依前列醇GM近20年前在美国最初获批用于PAH患者的长期持续输注;然而,该制剂在室温下稳定性有限,给药期间需要冷却或频繁更换药物。与依前列醇GM相比,依前列醇AS具有更长的热稳定性,这使得其在室温下可延长给药时间,且/或对配制好的溶液可进行冷藏保存。本文总结了依前列醇AS的药理学特性,并综述了其在成年PAH患者中的治疗应用。在临床试验中,依前列醇AS在血流动力学和症状转归方面提供了持续疗效,在从稳定的依前列醇GM治疗转换后以及在开放标签扩展研究期间,总体耐受性良好。此外,与依前列醇GM相比,依前列醇AS的治疗便利性显著提高。因此,依前列醇AS是一种有价值的治疗选择,有可能克服PAH患者长期静脉注射依前列醇治疗的一些局限性。