Tolcapone improves motor function in parkinsonian patients with the ''wearing-off'' phenomenon: A double-blind, placebo-controlled, multicenter trial
Tolcapone improves motor function in parkinsonian patients with the ''wearing-off'' phenomenon: A double-blind, placebo-controlled, multicenter trial
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DOI：
10.1212/wnl.49.4.1066
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发表时间：
1997-10-01
期刊：
影响因子：
9.9
通讯作者：
Pedder, S
中科院分区：
文献类型：
--
作者：
Rajput, AH;Martin, W;Pedder, S
我们在一项随机、双盲、平行组试验中研究了新型儿茶酚-O-甲基转移酶抑制剂托卡朋，100 和 200 毫克，每日 3 次 (tid)，该试验纳入了 202 名正在经历左旋多巴治疗“疗效减退”现象的帕金森病患者。 3个月后，与接受安慰剂治疗的患者相比，接受托卡朋治疗的患者平均每日左旋多巴剂量需求显着降低（p < 0.01）。在接受托卡朋 200 mg tid 治疗的患者中，通过患者日记测量的每日“停药”时间较基线减少了 3.25 小时；这种减少与安慰剂组中观察到的显着不同（p < 0.01）。此外，与安慰剂相比，托卡朋组每日左旋多巴摄入量显着减少（p < 0.01）。我们发现托卡朋组的运动功能和整体功效显着改善（p < 0.01）。最常见的不良事件与左旋多巴治疗有关。接受安慰剂的患者中有 18% 出现运动障碍或加重，接受托卡朋 100 mg tid 治疗的患者中有 51% 出现运动障碍，接受 200 mg tid 治疗的患者中有 64% 出现运动障碍，大多数病例发生在研究的前 30 天内。腹泻是最常见的非多巴胺能事件，安慰剂组的发生率为 14%，托卡朋 100 mg tid 组的发生率为 13%，托卡朋 200 mg tid 组的发生率为 19%。总共有 18% 的患者因不良事件退出：安慰剂组为 15%，托卡朋 100 mg tid 组为 17%，200 mg tid 组为 22%。我们得出的结论是，托卡朋作为一种辅助药物有望缓解左旋多巴治疗的帕金森病患者的“疗效减退”现象。
We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the ''wearing-off'' phenomenon on levodopa therapy. After 3 months, patients receiving tolcapone had a significant decrease in mean daily levodopa dose requirement compared with placebo-treated patients (p < 0.01). In patients treated with tolcapone 200 mg tid, daily ''off'' time, measured using patient diaries, was reduced from baseline by 3.25 hours; this reduction was significantly different from that seen in the placebo group (p < 0.01). Moreover, the number of daily levodopa intakes was reduced significantly in each tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor function and overall efficacy in the tolcapone groups (p < 0.01). The most frequent adverse events were associated with levodopa treatment. Dyskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving 200 mg tid, with most cases occurring within the first 30 days of the study. Diarrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17% on tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that tolcapone as an adjunct offers promise for the relief of the ''wearing-off'' phenomenon in levodopa-treated parkinsonian patients.