Hubble J P, Koller W C, Cutler N R, Sramek J J, Friedman J, Goetz C, Ranhosky A, Korts D, Elvin A
Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA.
Clin Neuropharmacol. 1995 Aug;18(4):338-47. doi: 10.1097/00002826-199508000-00006.
We evaluated the efficacy, safety, tolerability, and pharmacokinetics of pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease (PD). The study design was a parallel, placebo-controlled trial using an ascending dose of 4.5 mg/day pramipexole maximum. All subjects received selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who received at least one dose of the study medication, all but one, in the placebo group, completed the trial, which was 9 weeks in duration. The primary efficacy endpoints were changes in scores from baseline to final measurement on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The pramipexole group had a significantly greater improvement (p = 0.002) than the placebo group on UPDRS Part II (Activities of Daily Living). The change in score from baseline to final measurement on UPDRS Part III (Motor Examination) was not significantly different (p = 0.10) between the pramipexole and placebo groups, although the trend favoured the pramipexole group. All subjects in both the pramipexole and the placebo groups experienced one or more episodes of asymptomatic orthostatic hypotension; there was no significant difference between the pramipexole and the placebo groups in the number of subjects experiencing symptomatic orthostatic hypotension. The adverse events profile of pramipexole was similar, in general, to that of other dopamine receptor agonists. Plasma pramipexole levels increased linearly with dose. Pramipexole appears to be promising agent in the treatment of early PD.
我们评估了新型多巴胺D2受体激动剂普拉克索在早期帕金森病（PD）中的疗效、安全性、耐受性和药代动力学。研究设计为平行、安慰剂对照试验，普拉克索最大剂量为4.5毫克/天，剂量递增。所有受试者均接受司来吉兰（10毫克/天）治疗，但未接受左旋多巴治疗。在55名至少接受一剂研究药物的受试者中，除安慰剂组的一名受试者外，其余均完成了为期9周的试验。主要疗效终点是统一帕金森病评定量表（UPDRS）第二部分和第三部分从基线到最终测量的评分变化。在UPDRS第二部分（日常生活活动）中，普拉克索组的改善程度显著高于安慰剂组（p = 0.002）。尽管趋势有利于普拉克索组，但在UPDRS第三部分（运动检查）中，从基线到最终测量的评分变化在普拉克索组和安慰剂组之间无显著差异（p = 0.10）。普拉克索组和安慰剂组的所有受试者均经历了一次或多次无症状性直立性低血压发作；在经历症状性直立性低血压的受试者数量上，普拉克索组和安慰剂组之间无显著差异。普拉克索的不良事件谱总体上与其他多巴胺受体激动剂相似。血浆普拉克索水平随剂量呈线性增加。普拉克索似乎是治疗早期帕金森病的一种有前景的药物。
