Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations
Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations
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DOI：
10.1136/jnnp.60.1.36
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发表时间：
1996-01-01
影响因子：
11
通讯作者：
Rinne, UK
中科院分区：
文献类型：
--
作者：
Ruottinen, HM;Rinne, UK
目的：以双盲方式建立反复给药外周COMT抑制剂恩他卡酮的抗帕金森效应。方法：采用为期1个月的交叉研究。在两个为期四周的治疗期间，恩他卡彭（200毫克）或安慰剂与左旋多巴一起服用，每天4至10次。使用UPDRS的运动部分反复量化运动反应。测定血浆左旋多巴及其代谢物。结果：恩他卡彭通过降低左旋多巴外周o -甲基化和减缓其消除速率，延长了左旋多巴在血浆中的可用性，从而延长了左旋多巴进入大脑的时间，但不影响左旋多巴血浆最高浓度或达到最高浓度的时间。与药代动力学结果相对应，恩他卡彭与安慰剂相比，左旋多巴/DDC抑制剂个体剂量的运动反应持续时间延长了34分钟（24%,P = 0.001），运动障碍持续时间延长了39分钟（37%,P = 0.002），而不影响其强度或开始时间。恩他卡彭治疗导致运动障碍导致左旋多巴平均每日总剂量减少16%。此外，根据家庭日记，尽管左旋多巴的平均摄入量降低，但与安慰剂相比，平均每天的“开启”时间增加了2.1小时。结论：反复给药恩他卡彭辅助左旋多巴/DDC抑制剂治疗伴有左旋多巴相关波动的帕金森病的疗效得到证实。
Objectives-To establish, in a double blind manner, the antiparkinsonian effects of repeated dosing with entacapone, a peripheral COMT inhibitor.Methods-A one month, cross over study was conducted. During the two four-week treatment periods, entacapone (200 mg) or placebo was given with each levodopa dose four to 10 times daily. Motor responses were repeatedly quantified using the motor part of UPDRS. Plasma levodopa and its metabolites were measured.Results-Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate, without affecting the maximum plasma levodopa concentration or the time to maximum concentration. Corresponding with the pharmacokinetic findings, entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes (24%, P = 0.001) and dyskinesiae by 39 minutes (37%, P = 0.002) compared with placebo, without affecting their magnitude or starting time. Entacapone treatment resulted in a reduction of 16% in the mean total daily levodopa dose due to dyskinesiae. Also, according to the home diaries, the mean daily (''on'' time increased by 2.1 hours compared with placebo, despite the lowered mean levodopa intake.Conclusion-The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson's disease with levodopa related fluctuations is verified.