Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California 92350, USA.
Pharmacotherapy. 2009 Dec;29(12):1452-67. doi: 10.1592/phco.29.12.1452.
Rotigotine is a highly lipophilic dopamine-receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce "off" hours in levodopa-treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D(2) and D(3) receptors. With once-daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine-receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2-3 weeks, and the once-daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24-hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine-receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early-to-advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.
罗替高汀是一种高度亲脂性多巴胺受体激动剂，也是第一个经皮给药的药物，在早期帕金森病中单药治疗具有疗效和安全性，并减少晚期帕金森病患者接受左旋多巴治疗的“关期”时间。罗替高汀的药效基团是非麦角灵的，对多巴胺 D2 和 D3 受体具有高亲和力。每天应用一次，贴片基质在稳态时提供持续、无波动的血浆药物水平，从而导致持续、稳定的血浆和大脑水平以及纹状体多巴胺受体刺激。在早期帕金森病中，高达 8 毫克/24 小时的罗替高汀剂量与罗匹尼罗（高达 12 毫克/天）具有相当的疗效；在晚期帕金森病中，高达 16 毫克/24 小时的罗替高汀剂量与普拉克索（高达 4.5 毫克/天）具有相当的疗效和耐受性。在早期和晚期帕金森病的注册试验中，与罗替高汀最常观察到的不良反应是轻微的应用部位反应、头晕、恶心和嗜睡。经皮罗替高汀的剂量可在 2-3 周内滴定至维持剂量，每日一次的方案最大限度地减少了治疗的复杂性。当需要非口服给药时，经皮给药系统也是一个优势，24 小时持续、无波动的药物水平可以改善帕金森病的清晨和夜间症状。因此，经皮给予罗替高汀是多巴胺受体激动剂类别的一个临床创新和有用的补充。本综述总结了罗替高汀的关键药理学和临床数据，并为其在早期至晚期帕金森病中的应用提供了一个重点临床背景，同时也简要总结了其在不安腿综合征中的作用。
