Ruottinen H M, Rinne U K
Department of Neurology, University of Turku, Finland.
J Neurol Neurosurg Psychiatry. 1996 Jan;60(1):36-40. doi: 10.1136/jnnp.60.1.36.
To establish, in a double blind manner, the antiparkinsonian effects of repeated dosing with entacapone, a peripheral COMT inhibitor.
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.
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.
The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson's disease with levodopa related fluctuations is verified.
以双盲方式确定外周儿茶酚-O-甲基转移酶（COMT）抑制剂恩他卡朋重复给药的抗帕金森病作用。
进行了一项为期1个月的交叉研究。在两个为期4周的治疗期内，恩他卡朋（200mg）或安慰剂与每次左旋多巴剂量一起，每天给药4至10次。使用统一帕金森病评定量表（UPDRS）的运动部分对运动反应进行反复量化。测量血浆左旋多巴及其代谢产物。
恩他卡朋通过减少左旋多巴的外周O-甲基化并减慢其消除速率，延长了左旋多巴在血浆中的可用性，从而延长了其在脑中的可用性，而不影响血浆左旋多巴的最大浓度或达到最大浓度的时间。与药代动力学结果一致，与安慰剂相比，恩他卡朋使对单个左旋多巴/多巴脱羧酶（DDC）抑制剂剂量的运动反应持续时间延长了34分钟（24%，P = 0.001），使异动症持续时间延长了39分钟（37%，P = 0.002），而不影响其幅度或开始时间。恩他卡朋治疗使因异动症导致的每日左旋多巴平均总剂量减少了16%。此外，根据家庭日记，尽管左旋多巴摄入量降低，但与安慰剂相比，平均每日“开”期时间增加了2.1小时。
已证实恩他卡朋重复给药作为左旋多巴/DDC抑制剂治疗伴有左旋多巴相关波动的帕金森病的辅助药物的疗效。
