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罗匹尼罗:用于帕金森病管理的综述。

Ropinirole: a review of its use in the management of Parkinson's disease.

作者信息

Matheson A J, Spencer C M

机构信息

Adis International Limited, Auckland, New Zealand.

出版信息

Drugs. 2000 Jul;60(1):115-37. doi: 10.2165/00003495-200060010-00007.

Abstract

UNLABELLED

Ropinirole, a non-ergoline dopamine agonist, has selective affinity for dopamine D2-like receptors and little or no affinity for non-dopaminergic brain receptors. Ropinirole is indicated as adjunct therapy to levodopa in patients with advanced Parkinson's disease. It is also indicated, and recent clinical trials have focused on its use, as monotherapy in patients with early Parkinson's disease. In the symptomatic treatment of early Parkinson's disease ropinirole monotherapy was significantly more effective than placebo in 2 multicentre, randomised, double-blind trials of 3 to 12 months duration as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and Clinical Global Impression/Clinical Global Evaluation Scales. In a similarly designed 3-year comparative study with bromocriptine, ropinirole recipients showed a significant improvement in UPDRS- activities of daily living (ADL) scores; however, motor scores were similar between the 2 groups. Ropinirole and levodopa treatments were similar in efficacy as measured by UPDRS ADL scores, although ropinirole recipients showed significantly less improvement on UPDRS motor scores at the 5-year study end-point in a multicentre, randomised double-blind trial. As an adjunct therapy to levodopa in patients with more advanced Parkinson's disease, ropinirole was reported to be as effective as bromocriptine and significantly more effective than placebo. In general in the comparisons with placebo ropinirole allowed a > or =20% reduction in the concomitant dose of levodopa without compromising efficacy in a significant proportion of patients and, in some trials decreased the amount of awake time spent in the 'off' state ('off' state is defined as a gradual return to parkinsonism despite adequate medication). Ropinirole was well tolerated either as monotherapy or as an adjunct to levodopa treatment. Nausea, dizziness and somnolence were the most commonly reported adverse events and were reported at a higher incidence by patients receiving ropinirole than by those receiving placebo. In patients with early Parkinson's disease, ropinirole generally showed a similar overall tolerability profile to bromocriptine although, over a 3-year period nausea was more commonly reported with ropinirole recipients. In a 5-year study, the incidence of dyskinesia was significantly lower with ropinirole than with levodopa regardless of levodopa supplementation. Prior to the addition of supplementary levodopa 5% of ropinirole recipients had experienced dyskinesia compared with 36% of those receiving levodopa.

CONCLUSIONS

In patients with early Parkinson's disease, ropinirole monotherapy was more efficacious than bromocriptine with regard to improvement in activities of daily living, and need for supplemental levodopa. Ropinirole recipients had a higher requirement for levodopa supplementation than levodopa recipients in a 5-year study, but the incidence of dyskinesia was significantly lower with ropinirole than with levodopa (markedly so in the one third of ropinirole recipients who were able to remain on monotherapy with no levodopa supplementation). Thus available data suggest that ropinirole may provide a means of treating early Parkinson's disease while minimising the risk of dyskinesia and delaying the need for supplemental levodopa in some patients. In addition, ropinirole is also efficacious in the management of more advanced Parkinson's disease in patients who are experiencing motor complications after long term levodopa use.

摘要

未标注

罗匹尼罗是一种非麦角碱多巴胺激动剂,对多巴胺D2样受体具有选择性亲和力,对非多巴胺能脑受体几乎没有或没有亲和力。罗匹尼罗被用作晚期帕金森病患者左旋多巴的辅助治疗。它也被用作早期帕金森病患者的单一疗法,并且最近的临床试验也集中在这方面的应用。在早期帕金森病的症状治疗中,在两项为期3至12个月的多中心、随机、双盲试验中,根据统一帕金森病评定量表(UPDRS)运动评分和临床总体印象/临床总体评估量表评估,罗匹尼罗单一疗法比安慰剂显著更有效。在一项与溴隐亭设计相似的3年比较研究中,接受罗匹尼罗治疗的患者在UPDRS日常生活活动(ADL)评分上有显著改善;然而,两组之间的运动评分相似。根据UPDRS ADL评分衡量,罗匹尼罗和左旋多巴治疗的疗效相似,尽管在一项多中心、随机双盲试验的5年研究终点,接受罗匹尼罗治疗的患者在UPDRS运动评分上的改善明显较少。作为更晚期帕金森病患者左旋多巴的辅助治疗,据报道罗匹尼罗与溴隐亭效果相同,且比安慰剂显著更有效。总体而言,在与安慰剂的比较中,罗匹尼罗在不影响相当一部分患者疗效的情况下,可使左旋多巴的伴随剂量减少≥20%,并且在一些试验中减少了处于“关”状态(“关”状态定义为尽管用药充足但逐渐恢复帕金森症状)的清醒时间。罗匹尼罗作为单一疗法或左旋多巴治疗的辅助药物耐受性良好。恶心、头晕和嗜睡是最常报告的不良事件,接受罗匹尼罗治疗的患者报告的发生率高于接受安慰剂治疗的患者。在早期帕金森病患者中,罗匹尼罗总体耐受性与溴隐亭相似,尽管在3年期间接受罗匹尼罗治疗的患者更常报告恶心。在一项5年研究中,无论是否补充左旋多巴,罗匹尼罗导致的运动障碍发生率均显著低于左旋多巴。在添加补充左旋多巴之前,5%接受罗匹尼罗治疗的患者出现运动障碍,而接受左旋多巴治疗的患者为36%。

结论

在早期帕金森病患者中,就日常生活活动改善和补充左旋多巴的需求而言,罗匹尼罗单一疗法比溴隐亭更有效。在一项5年研究中,接受罗匹尼罗治疗的患者比接受左旋多巴治疗的患者对补充左旋多巴的需求更高,但罗匹尼罗导致的运动障碍发生率显著低于左旋多巴(在三分之一能够不补充左旋多巴而维持单一疗法的罗匹尼罗治疗患者中尤为明显)。因此,现有数据表明,罗匹尼罗可能为治疗早期帕金森病提供一种方法,同时将运动障碍风险降至最低,并在一些患者中延迟补充左旋多巴的需求。此外,罗匹尼罗对长期使用左旋多巴后出现运动并发症的更晚期帕金森病患者的治疗也有效。

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