High levodopa plasma concentration after oral administration predicts levodopa-induced dyskinesia in Parkinson's disease
High levodopa plasma concentration after oral administration predicts levodopa-induced dyskinesia in Parkinson's disease
复制标题
口服给药后左旋多巴血浆浓度高可预测帕金森病中左旋多巴引起的运动障碍
DOI：
10.1016/j.parkreldis.2020.05.022
复制
发表时间：
2020
影响因子：
4.1
通讯作者：
Yuji Takahashi
中科院分区：
文献类型：
--
作者：
Tomotaka Shiraishi;Noriko Nishikawa;Yohei Mukai;Yuji Takahashi
在帕金森病（PD）患者中，脉动性多巴胺能刺激可能是左旋多巴诱导的运动障碍（LID）的主要原因。目的探讨PD患者左旋多巴药代动力学（PK）与LID的相关性。方法回顾性分析连续255例无LID的PD患者，使用100 mg左旋多巴进行PK评估。通过左旋多巴常用处方（卡比多巴10 mg [n = 185]和苯拉西嗪25 mg [n = 70]）确定PK评估中使用的外周脱羧酶抑制剂类型。结果中位随访32个月（IQR， 16-49个月），73例（29%）患者发生LID。与未发生LID （PD-LID−）的患者相比，发生LID （PD-LID +）的患者更年轻（p = 0.003），最大左旋多巴浓度（Cmax） （p = 0.002）、曲线下面积（p < 0.001）、LEDD （p < 0.001）和运动症状改善（p = 0.009）均显著提高。在多变量Cox比例风险模型中，Cmax和AUC与事件LID相关（风险比[HR] 1.11, 95%可信区间[CI] 1.03-1.19，风险比[HR] 1.13, 95% CI 1.03-1.24）。此外，年龄较小、苯塞拉肼的使用、LEDD和MAOBI的使用与LID的发生有关。结论PD患者口服左旋多巴后高血药浓度与发生LID有关。
IntroductionIn patients with Parkinson's disease (PD), pulsatile dopaminergic stimulation may be a primary cause of levodopa-induced dyskinesia (LID). We aimed to investigate the correlation between levodopa pharmacokinetics (PK) and LID in PD.MethodsWe retrospectively reviewed the consecutive series of 255 PD patients without LID who underwent PK assessments with 100 mg levodopa. The type of peripheral decarboxylase inhibitor used in the PK assessments was determined by the usual prescription of the formulations of levodopa (10 mg carbidopa [n = 185] and 25 mg benserazide [n = 70]).ResultsDuring a median follow-up of 32 months (IQR, 16–49 months), 73 patients (29%) developed LID. Compared with patients who did not develop LID (PD–LID−), those who developed LID (PD–LID+) were younger (p = 0.003) and had significantly higher maximum levodopa concentration (Cmax) (p = 0.002) and area under the curve (p < 0.001), LEDD (p < 0.001), and improvement of motor symptoms (p = 0.009). In the multivariate Cox proportional hazards models, Cmax and AUC were associated with incident LID (Hazard Ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.19 and HR 1.13, 95% CI 1.03–1.24, respectively). In addition, younger age, benserazide use, LEDD, and MAOBI use were associated with incident LID.ConclusionHigh levodopa plasma concentration after oral administration was associated with incident LID in patients with PD.