Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
CNS-Campus Neurológico Sénior, Torres Vedras, Portugal.
Mov Disord. 2022 Nov;37(11):2272-2283. doi: 10.1002/mds.29193. Epub 2022 Aug 31.
Inhibiting catechol-O-methyltransferase extends the plasma half-life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations.
To evaluate the effects of once-daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens.
A total of 24 patients with PD and motor fluctuations were enrolled in an exploratory, open-label, modified cross-over trial. Participants first received levodopa/carbidopa 500/125 mg (five intakes) for 2 weeks and were then randomly assigned (1:1) to levodopa/carbidopa 400/100 mg given over either four or five daily intakes plus opicapone 50 mg for an additional 2 weeks. Levodopa 12-hour pharmacokinetics was the primary outcome (ie, excluding the effect of last/evening levodopa/carbidopa intake), with motor complications evaluated as secondary outcomes.
Over 12-hour pharmacokinetics and compared with five-intake levodopa/carbidopa 500/125 mg without opicapone, maximal levodopa concentrations were similar or nonsignificantly higher on both levodopa/carbidopa 400/100 mg regimens plus opicapone. Despite a 100 mg lower total levodopa/carbidopa daily dose, adding opicapone 50 mg at least doubled the levodopa plasma half-life and minimal concentrations, with a significant ≈30% increase in total exposure. The levodopa fluctuation index was only significantly lower for the five intakes plus opicapone regimen (difference of -71.8%; P < 0.0001). Modifications to levodopa pharmacokinetics were associated with decreased off time and increased on time.
Combining opicapone 50 mg with a 100 mg lower daily dose of levodopa provides higher levodopa bioavailability with avoidance of trough levels. Despite the lower levodopa dose, modifying the levodopa pharmacokinetic profile with opicapone was associated with decreased off time and increased on time. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
抑制儿茶酚-O-甲基转移酶可延长左旋多巴的血浆半衰期，这可能使医生能够优化帕金森病（PD）患者的左旋多巴治疗方案，使其出现运动波动。
评估每日一次的opicapone 对添加到两种不同左旋多巴给药方案时左旋多巴血浆药代动力学和运动反应的影响。
共纳入 24 例伴有运动波动的 PD 患者，进行一项探索性、开放标签、改良交叉试验。参与者首先接受左旋多巴/卡比多巴 500/125mg（5 次剂量）治疗 2 周，然后随机（1:1）分配至左旋多巴/卡比多巴 400/100mg 治疗，每日 4 次或 5 次剂量，另加 opicapone 50mg，治疗 2 周。左旋多巴 12 小时药代动力学为主要结局（即排除最后/夜间左旋多巴/卡比多巴摄入的影响），运动并发症为次要结局。
在 12 小时药代动力学方面，与不含 opicapone 的左旋多巴/卡比多巴 500/125mg 相比，两种左旋多巴/卡比多巴 400/100mg 方案加用 opicapone 后，最大左旋多巴浓度相似或无显著升高。尽管每日左旋多巴/卡比多巴总剂量降低 100mg，但加用 opicapone 50mg 可使左旋多巴血浆半衰期和最小浓度至少增加一倍，总暴露量显著增加约 30%。左旋多巴波动指数仅在 5 次剂量加用 opicapone 方案中显著降低（差值-71.8%；P < 0.0001）。左旋多巴药代动力学的改变与减少关期和增加开期有关。
将 opicapone 50mg 与每日左旋多巴剂量降低 100mg 联合应用可提高左旋多巴的生物利用度，避免谷值水平。尽管左旋多巴剂量较低，但用 opicapone 改变左旋多巴药代动力学特征与减少关期和增加开期有关。
