罗替高汀透皮贴剂在帕金森病中的应用：药理学、临床证据、特殊人群管理及卫生经济学的叙述性综述

文献信息

中文摘要

背景： 帕金森病（PD）需要终身多巴胺能治疗，但口服途径常因胃肠道功能障碍、吞咽困难和围手术期禁食而受限。突然停用口服多巴胺能药物可能诱发严重的运动功能恶化或帕金森综合征-高热综合征。罗替高汀透皮贴剂通过非麦角类多巴胺激动剂（DA）制剂提供24小时持续多巴胺能刺激（CDS），绕过首过代谢和胃肠道吸收，在口服多巴胺能给药变得不可靠或不可能时可能特别有用。
目的： 综合已发表的关于罗替高汀药理学、临床疗效、脆弱人群管理、安全性、真实世界有效性和卫生经济学的证据，重点在于相对于既往一般性综述，基于情景、纳入亚洲/中国以及面向药学的叙述性综述的增量贡献。
方法： 通过结构化文献检索和书目筛选，对随机对照试验、荟萃分析、监管文件、药物经济学模型和前瞻性观察性研究进行叙述性综述。
结果： 透皮生物利用度约为37%，而口服罗替高汀低于5%。关键的中国试验SP0914（早期PD：UPDRS II + III -4.9 vs. -0.2）和SP1037（晚期PD：安慰剂校正的关期减少 -1.20 小时/天 [95% CI -1.83 至 -0.57]；组内变化 -2.36 小时/天）证明了疗效；荟萃分析支持运动和部分非运动获益，包括睡眠、情绪和胃肠道耐受性，而吞咽相关信号仍为初步性，主要基于小型观察性研究。围手术期禁食、吞咽困难、终末期疾病和肝肾功能损害是临床上重要的情景，在这些情景中可考虑非口服给药，尽管关键运动试验之外的 supporting evidence 往往有限。应用部位反应（ASRs）是主要的局部不良事件；结构化的14天部位轮换将ASR从50.0%降至20.3%（P = 0.0373）。中国的成本-效果分析报告，与市场价格的普拉克索速释剂相比，每质量调整生命年的增量成本-效果比为1,118,617.81元人民币，价格敏感性阈值为降价28.5%和9.5%。
结论： 当口服给药不可靠时，罗替高汀为PD患者提供CDS；有必要进行个体化患者选择、结构化药学服务和更新的药物经济学评价。

英文摘要

BACKGROUND: Parkinson's disease (PD) requires lifelong dopaminergic therapy, yet oral routes are frequently compromised by gastrointestinal dysfunction, dysphagia, and perioperative fasting. Abrupt withdrawal of oral dopaminergic drugs may precipitate severe motor deterioration or parkinsonism-hyperpyrexia syndrome. Rotigotine transdermal patch delivers 24-h continuous dopaminergic stimulation (CDS) via a non-ergot dopamine agonist (DA) formulation that bypasses first-pass metabolism and gastrointestinal absorption, and may be particularly useful when oral dopaminergic delivery becomes unreliable or is not possible.
OBJECTIVE: To synthesize published evidence on rotigotine pharmacology, clinical efficacy, management in vulnerable populations, safety, real-world effectiveness, and health economics, with emphasis on the incremental contribution of a scenario-based, Asia/China-inclusive, and pharmacy-oriented narrative relative to prior general reviews.
METHODS: Narrative review of randomized controlled trials, meta-analyses, regulatory documents, pharmacoeconomic models, and prospective observational studies identified through structured literature search and bibliographic screening.
RESULTS: Transdermal bioavailability is approximately 37% versus less than 5% for oral rotigotine. Pivotal Chinese trials SP0914 (early PD: UPDRS II + III -4.9 vs. -0.2) and SP1037 (advanced PD: placebo-adjusted off-time reduction -1.20 h/d [95% CI -1.83 to -0.57]; within-group change -2.36 h/d) demonstrated efficacy; meta-analyses support motor and selected non-motor benefits, including sleep, mood, and gastrointestinal tolerability, whereas swallowing-related signals remain preliminary and based mainly on small observational studies. Perioperative fasting, dysphagia, end-stage disease, and hepatorenal impairment represent clinically important scenarios in which non-oral delivery may be considered, although supporting evidence outside pivotal motor trials is often limited. Application-site reactions (ASRs) are the principal local adverse events; structured 14-day site rotation reduced ASR from 50.0% to 20.3% (P = 0.0373). Chinese cost-effectiveness analyses reported an incremental cost-effectiveness ratio of 1,118,617.81 CNY per quality-adjusted life year versus pramipexole immediate-release at market price, with price-sensitivity thresholds of 28.5% and 9.5% reductions.
CONCLUSION: Rotigotine provides CDS for patients with PD when oral delivery is unreliable; individualized patient selection, structured pharmaceutical care, and updated pharmacoeconomic evaluation are warranted.