Poplawska-Domaszewicz Karolina, Batzu Lucia, Falup-Pecurariu Cristian, Chaudhuri K Ray
Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Parkinson's Foundation Centre of Excellence, King's College Hospital, London, UK.
Neurol Ther. 2024 Aug;13(4):1055-1068. doi: 10.1007/s40120-024-00635-4. Epub 2024 Jun 14.
The management of Parkinson's disease (PD) continues to evolve with advancements in non-oral levodopa-based therapies aiming to provide continuous drug delivery (CDD). Such therapies address the challenges posed by the emergence of motor fluctuations, dyskinesias, and non-motor fluctuations (NMF) associated with oral levodopa administration and contributing to define the advanced stage of PD. The key focus of this review is placed on subcutaneous foslevodopa/foscarbidopa (Foslevodopa/foscarbidopa) infusion, showcasing its recent clinical availability and efficacy in providing continuous levodopa delivery. While providing an overview of the other non-oral levodopa-based CDD systems, such as intrajejunal levodopa-carbidopa infusion and levodopa-entacapone-carbidopa infusion, we highlight the current promising evidence for Foslevodopa/foscarbidopa to improve, for example, "on time" without troublesome dyskinesia and reducing "off time" in people with advanced PD. Additionally, Foslevodopa/foscarbidopa demonstrates potential in managing early morning off periods, sleep quality and other motor and non-motor symptoms. Moreover, other non-oral CDD options such as ND0612 and DIZ102/DIZ101 are discussed, with focus on their pharmacokinetics/pharmacodynamics, efficacy, and safety profiles. While these advancements present new therapeutic avenues, long-term observational studies are warranted to elucidate their impact on existing PD therapies. Overall, this review provides insights into the evolving landscape of non-oral CDD therapies and offers a pragmatic approach for their integration into clinical practice.
随着旨在实现持续药物递送（CDD）的非口服左旋多巴类疗法的进展，帕金森病（PD）的管理不断发展。此类疗法应对了与口服左旋多巴给药相关的运动波动、异动症和非运动波动（NMF）的出现所带来的挑战，这些波动有助于定义PD的晚期阶段。本综述的重点是皮下注射福沙左旋多巴/福沙卡比多巴（Foslevodopa/foscarbidopa），展示其近期的临床可用性以及在提供持续左旋多巴递送方面的疗效。在概述其他基于非口服左旋多巴的CDD系统（如空肠内左旋多巴-卡比多巴输注和左旋多巴-恩他卡朋-卡比多巴输注）时，我们强调了福沙左旋多巴/福沙卡比多巴目前在改善例如“开期”时间且无麻烦的异动症以及减少晚期PD患者的“关期”时间方面的有前景的证据。此外，福沙左旋多巴/福沙卡比多巴在管理清晨关期、睡眠质量以及其他运动和非运动症状方面显示出潜力。此外，还讨论了其他非口服CDD选项，如ND0612和DIZ102/DIZ101，重点关注它们的药代动力学/药效学、疗效和安全性概况。虽然这些进展提供了新的治疗途径，但仍需要长期观察性研究来阐明它们对现有PD疗法的影响。总体而言，本综述深入探讨了非口服CDD疗法不断变化的格局，并为将其整合到临床实践中提供了务实的方法。
