Blindauer Karen, Shoulson Ira, Oakes David, Kieburtz Karl, Schwid Steven, Fahn Stanley, Stern Matthew, Goetz Christopher, Nutt John, Goren Sari, Sayag Naim, Scolnik Marisa, Levy Ruth, Eyal Eli, Salzman Phyllis, Pagano Mary
Department of Neurology, Medical College of Wisconsin, Milwaukee 53226, USA.
Arch Neurol. 2006 Feb;63(2):210-6. doi: 10.1001/archneur.63.2.210.
Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration.
To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations.
A double-blind, randomized, comparative clinical trial.
Forty-four sites in the United States and Canada.
Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing.
Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks.
Change from baseline in total daily TTON as measured using home diaries.
The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias.
Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.
运动波动是帕金森病（PD）患者长期接受左旋多巴治疗时常见的并发症。左旋多巴在胃肠道中胃排空缓慢且溶解性差，可能会延迟给药后药物起效时间。乙磺半胱氨酸是左旋多巴的乙酯前体药物，其在胃中的溶解性更高，能迅速进入小肠，快速水解为左旋多巴，达到最大左旋多巴浓度的时间缩短。
确定乙磺半胱氨酸对有运动波动的PD患者的疗效、安全性和耐受性。
一项双盲、随机、对照临床试验。
美国和加拿大的44个地点。
327例PD患者，左旋多巴给药后每日总“开”期（TTON）潜伏期至少90分钟。
乙磺半胱氨酸-卡比多巴或左旋多巴-卡比多巴治疗18周。
使用家庭日记测量的每日总TTON相对于基线的变化。
乙磺半胱氨酸-卡比多巴组从基线到治疗期间平均每日总TTON减少0.58小时，左旋多巴-卡比多巴组减少0.79小时（P = 0.24）。乙磺半胱氨酸-卡比多巴组和左旋多巴-卡比多巴组在缓解反应失败方面无显著差异（-6.82%对-4.69%；P = 0.20）。乙磺半胱氨酸-卡比多巴组（-0.85小时）和左旋多巴-卡比多巴组（-...
