UT Southwestern, Dallas, TX.
University of Colorado, Denver, CO.
Am Heart J. 2014 Feb;167(2):218-225.e1. doi: 10.1016/j.ahj.2013.08.008. Epub 2013 Oct 16.
Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM.
In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study.
Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively.
In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated.
含有精氨酸甘露醇赋形剂的依前列醇钠（依前列醇 AM；Veletri [Actelion Pharmaceuticals Ltd，瑞士 Allschwil]）和含有甘氨酸甘露醇赋形剂的依前列醇钠（依前列醇 GM；Flolan [GlaxoSmithKline，北卡罗来纳州三角公园]）均为治疗肺动脉高压（PAH）的静脉内治疗药物。依前列醇 AM 含有不同的无活性赋形剂，与依前列醇 GM 相比，在室温下更稳定。
在这项前瞻性、多中心、开放性、随机、IV 期探索性研究中，需要注射用前列环素治疗的依前列醇初治患者按 2:1 比例随机分配至开放性依前列醇 AM 或依前列醇 GM 治疗组。研究期为 28 天，随后进行 30 天的安全性随访。研究目的是描述性比较依前列醇 AM 和依前列醇 GM 在 PAH 中的安全性、耐受性、药物代谢产物水平和治疗效果。由于研究的探索性质，仅进行描述性统计分析。
30 名 PAH 患者（18-70 岁，24 名女性，20 名特发性 PAH）被随机分配至依前列醇 AM 组（n = 20）或依前列醇 GM 组（n = 10）。最常报告的不良事件包括下颌痛、头痛、恶心和潮红。研究期间发生 2 例死亡，随访期间发生 1 例死亡，均发生在接受依前列醇 AM 治疗的患者中。所有死亡均被主治医生归类为与依前列醇 AM 无关。依前列醇 AM 组和依前列醇 GM 组分别从基线到第 28 天 6 分钟步行距离的中位数（范围）变化为 36 m（-127 至 210 m）和 49 m（-44 至 110 m）。
在这项依前列醇 AM 治疗 PAH 的随机临床试验中，该新型制剂的使用具有更好的室温稳定性，且耐受性良好。
