Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA.
Clintrex Research Corporation, Sarasota, Florida, USA.
Mov Disord. 2024 Jun;39(6):945-954. doi: 10.1002/mds.29824. Epub 2024 May 2.
Double-blind studies have demonstrated that motor complications in Parkinson's disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth.
Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations.
This was a 2-week, open-label study (NCT04778176) in 16 PD patients treated with ≥4 levodopa doses/day and experiencing motor fluctuations. On Day 1 (clinic setting) patients received their usual dose of standard LD/CD; DopaFuse therapy was initiated on Day 2, and on Day 3 patients received DopaFuse plus a morning oral LD/CD dose. Patients returned home on Days 4-14 and returned for in-clinic assessment on Day 15.
Continuous DopaFuse delivery of LD/CD was associated with reduced variability in plasma levodopa levels compared to oral LD/CD (mean ± SD levodopa Fluctuation Index reduced from 2.15 ± 0.59 on Day1 to 1.50 ± 0.55 on Day 2 (P = 0.0129) and to 1.03 ± 0.53 on Day 3 (P < 0.0001)). This pharmacokinetic improvement translated into significantly reduced OFF time with DopaFuse therapy (reduction of -1.72 ± 0.37 h at Day 15; P = 0.0004) and increased ON time without severe dyskinesias (increase of 1.72 ± 0.37 h at Day 15; P = 0.0004) versus oral LD/CD administration. DopaFuse therapy was not associated with any clinically significant adverse events.
Continuous delivery of LD/CD using the DopaFuse system was associated with significantly less variability in plasma levodopa concentrations and reductions in OFF time compared to treatment with standard oral LD/CD therapy and was well tolerated. © 2024 International Parkinson and Movement Disorder Society.
双盲研究表明，通过持续输送左旋多巴可以减少帕金森病（PD）患者的运动并发症。DopaFuse 系统是一种新型口腔内微泵，可附着在保持器上，并使用推进剂将左旋多巴/卡比多巴（LD/CD）连续输送到口腔中。
评估与 PD 患者间歇性口服标准 LD/CD 治疗相比，使用 DopaFuse 系统输送 LD/CD 的安全性、药代动力学和疗效，这些患者存在运动波动。
这是一项为期 2 周的开放标签研究（NCT04778176），纳入了 16 名每天服用≥4 剂左旋多巴且存在运动波动的 PD 患者。第 1 天（诊所环境），患者接受标准 LD/CD 的常用剂量；第 2 天开始 DopaFuse 治疗，第 3 天患者接受 DopaFuse 加早晨口服 LD/CD 剂量。患者在第 4-14 天回家，并在第 15 天返回诊所评估。
与口服 LD/CD 相比，连续 DopaFuse 输送 LD/CD 可降低血浆左旋多巴水平的变异性（平均±SD 左旋多巴波动指数从第 1 天的 2.15±0.59 降低到第 2 天的 1.50±0.55（P=0.0129）和第 3 天的 1.03±0.53（P<0.0001））。这种药代动力学改善转化为使用 DopaFuse 治疗显著减少 OFF 时间（第 15 天减少-1.72±0.37 小时；P=0.0004）和增加无严重运动障碍的 ON 时间（第 15 天增加 1.72±0.37 小时；P=0.0004），与口服 LD/CD 给药相比。DopaFuse 治疗与任何临床显著的不良事件无关。
与标准口服 LD/CD 治疗相比，使用 DopaFuse 系统持续输送 LD/CD 与血浆左旋多巴浓度的变异性显著降低和 OFF 时间减少相关，且耐受性良好。© 2024 国际帕金森病和运动障碍学会。
