University "G. d'Annunzio" of Chieti-Pescara, Department of Neuroscience, Imaging and Clinical Sciences , Via dei Vestini 31, Chieti, 66100 , Italy
Expert Opin Drug Metab Toxicol. 2015 Feb;11(2):295-306. doi: 10.1517/17425255.2015.993315. Epub 2014 Dec 16.
Multiple sclerosis (MS) is the most frequent cause of neurological impairment and sustained disability in young adults. Currently approved disease-modifying drugs do not directly ameliorate the most common symptoms, such as walking impairment. Dalfampridine (DAL), currently approved in all forms of MS, might represent an answer to unmet needs in the symptomatic treatment of MS.
The main pharmacological and clinical properties and safety issues of DAL, an extended-release formulation of 4-aminopyridine (4-AP), a broad-spectrum voltage-dependent potassium channel blocker, are described. Relevant publications were identified from a search of PubMed from 1966 to June 2014 (search terms 'dalfampridine OR fampridine OR 4-aminopyridine). DAL, 10 mg twice daily, improves walking ability in approximately one-third and walking speed in about 25% of patients, independently from disease course, compared with placebo; it also improves leg strength. Treatment is generally well tolerated, although there is a dose-dependent increased risk of seizures, especially with dosages > 10 mg twice daily.
DAL represents an option in the symptomatic treatment of MS. Improved ambulation can impact quality of life, motivation and adherence, enhancing the successful management of MS. It has still to be established whether this favorably impacts costs associated with MS.
多发性硬化症(MS)是导致年轻人神经功能障碍和持续性残疾的最常见原因。目前批准的疾病修正药物并不能直接改善最常见的症状,如行走障碍。地夫可特(DAL)目前在所有形式的多发性硬化症中都被批准使用,它可能是治疗多发性硬化症症状未满足需求的一种答案。
本文描述了地夫可特(一种广泛的电压依赖性钾通道阻滞剂 4-氨基吡啶[4-AP]的缓释制剂)的主要药理学和临床特性以及安全性问题。从 1966 年到 2014 年 6 月,通过 PubMed 搜索了相关文献(搜索词为“地夫可特或苯丙胺或 4-氨基吡啶”)。与安慰剂相比,每日两次服用 10 毫克地夫可特可使约三分之一的患者行走能力和大约 25%的患者行走速度得到改善;它还能改善腿部力量。治疗通常耐受性良好,尽管存在剂量依赖性癫痫发作风险增加,特别是每日两次服用剂量大于 10 毫克时。
地夫可特是多发性硬化症症状治疗的一种选择。改善步行能力可以影响生活质量、动力和依从性,从而增强多发性硬化症的成功管理。它是否能有利地影响与多发性硬化症相关的成本仍有待确定。