BackgroundDouble‐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.ObjectivesEvaluate 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.MethodsThis 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.ResultsContinuous 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.ConclusionsContinuous 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.

中文翻译：

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使用口腔内微泵系统连续左旋多巴给药：开放标签药代动力学和临床研究

背景双盲研究表明，持续给予左旋多巴可以减少帕金森病（PD）的运动并发症。 DopaFuse 系统是一种新型口腔内微型泵，连接到固定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。 目标评估通过 DopaFuse 系统输送的 LD/CD 的安全性、药代动力学和功效与间歇剂量的标准口服 LD/CD 治疗出现运动波动的 PD 患者进行比较。方法这是一项为期 2 周的开放标签研究 (NCT04778176)，受试者为 16 名接受 ≥ 4 剂量/天左旋多巴治疗且出现运动波动的 PD 患者。第 1 天（临床环境）患者接受常规剂量的标准 LD/CD； DopaFuse 治疗从第 2 天开始，第 3 天患者接受 DopaFuse 加早晨口服 LD/CD 剂量。患者在第 4-14 天返回家中，并在第 15 天返回进行临床评估。 结果与口服 LD/CD 相比，连续 DopaFuse 递送 LD/CD 与血浆左旋多巴水平变异性降低相关（平均值 ± SD 左旋多巴波动指数从第 1 天为 2.15 ± 0.59，第 2 天为 1.50 ± 0.55（磷= 0.0129) 并在第 3 天达到 1.03 ± 0.53 (磷< 0.0001))。这种药代动力学的改善转化为 DopaFuse 治疗的关闭时间显着减少（第 15 天减少 -1.72 ± 0.37 小时；磷= 0.0004），并且 ON 时间增加，无严重运动障碍（第 15 天增加 1.72 ± 0.37 小时；磷= 0.0004) 与口服 LD/CD 给药相比。 DopaFuse 治疗与任何临床上显着的不良事件无关。结论与标准口服 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着降低以及关闭时间的减少相关，并且效果良好容忍的。 © 2024 国际帕金森和运动障碍协会。