Cogent Biosciences, Waltham, MA.
Massachusetts College of Pharmacy and Health Sciences, School of Pharmacy, Manchester, NH; and.
Am J Ther. 2024;31(3):e258-e267. doi: 10.1097/MJT.0000000000001742.
Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.
The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.
Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.
The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.
Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.
肌萎缩侧索硬化症（ALS）的特征是由于大脑和脊髓内的神经细胞退化导致运动神经元丧失。早期症状包括四肢无力、抽搐或肌肉痉挛以及言语含糊。随着疾病的发展，呼吸困难、吞咽困难和瘫痪可能导致死亡。目前，尚无治愈 ALS 的药物，指南建议侧重于症状管理的治疗方法。依达拉奉于 2017 年被美国食品和药物管理局（FDA）批准为减缓 ALS 进展的治疗药物。2022 年 5 月，FDA 批准了依达拉奉的口服混悬剂（ORS）制剂。
依达拉奉的作用机制尚未明确。然而，其神经保护作用被认为是通过消除自由基产生的抗氧化特性产生的。
与依达拉奉静脉注射（60mg）相比，依达拉奉 ORS（105mg）的生物利用度为 57%。ORS 应在早上空腹服用，用清水送服，1 小时内不要进食或饮用任何东西。依达拉奉与白蛋白（92%）结合，平均分布容积为 63.1L，半衰期为 4.5-9 小时，静脉给药后总清除率为 35.9L/h。依达拉奉代谢为无活性的硫酸盐和葡萄糖醛酸缀合物。
FDA 的批准基于依达拉奉 ORS 的药代动力学、安全性、耐受性和生物利用度研究。一项针对 185 名 ALS 患者的全球、多中心、开放性安全性研究，对依达拉奉 ORS 进行了为期 48 周的研究。报告最多的治疗后出现的不良事件是跌倒、肌肉无力和便秘。严重的治疗后出现的不良事件包括病情恶化、吞咽困难、呼吸困难和呼吸衰竭。
口服依达拉奉是一种 ALS 治疗药物，可以由患者自己或护理人员给药，无需在医疗机构由医疗保健专业人员给药。
