国产托卡朋片治疗帕金森病有效性及安全性的临床研究

The efficacy and safety of tolcapone in the treatment of patients with Parkinson's disease

目的评价国产托卡朋片剂治疗帕金森病(PD)的有效性及安全性。方法观察PD患者80例,采用随机、双盲、安慰剂对照、平行分组研究。将PD患者随机分为托卡朋片治疗组和安慰剂组,每组40例,给予观察药物托卡朋片或安慰剂1片,每天3次,总观察时间为26周。主要疗效指标采用国际通用的评价PD症状的UPDRS评分。次要疗效指标是包括“关”的时间缩短,正在接受左旋多巴制剂治疗的患者从基线到试验结束时,每日左旋多巴制剂剂量减少。结果对稳定性PD患者治疗26周,服用托卡朋片组PD患者的UPDRS评分较安慰剂组明显降低(P<0.01)。用于伴有症状波动的患者:80例PD患者中,有明显“开-关”现象者21例,服用托卡朋组与安慰剂组相比,“关期”平均减少38%、“开期”平均延长22%,有68%伴有剂末现象的PD患者服用托卡朋后出现剂末现象减少,而只有37%伴有剂末现象的PD患者服用安慰剂后出现剂末现象减少(P<0.01)。其中12例口服左旋多巴制剂的患者,加服托卡朋后有5例该制剂减量。患者加用托卡朋前、后,血尿常规,肝肾功能检查结果皆在正常范围内,心率、血压和心电图无明显变化。80例中有35例出现不同类型的不良反应,托卡朋组75%、安慰剂组45%,差异非常显著(P<0.01)。患者出现的异动症、恶心、厌食、肌阵挛、失眠等副作用在减少左旋多巴制剂的用量时,副作用大大降低或消失。结论COMT抑制剂托卡朋能够改善PD患者的运动功能,是治疗PD有效的辅助药物,在波动性PD患者中可出现“关期”的时限缩短,“开期”时限的增加。

Objective To assess the efficacy and safety of tolcapone in the treatment of Parkinson＇s disease （PD） .Methods Eighty patients with PD were followed up by a multicentre, double-blind, placebo-controlled, randomized method for 26 weeks. UPDRS score was used to evaluate efficacy of tolcapone in the treatment of PD. Results Application in stable PD patients： tolcapone 100 mg or placebo, t. i. d, for 26 weeks. UPDRS score in tolcapone group was significantly lower than that in placebo group （ P 〈 0.01 ）. Patients with motor fluctuations： among the 80 PD cases,21 cases had ＂on/off＂. As compared with that of placebo group, the ＂off＂ time of patients in tolcapone group reduced by 38 % averagely, the ＂on＂ time prolonged by 22 % averagely. The wearing-off phenomenon reduced in 68% patients of tolcapone group,but which reduced in only 37% patients in placebo group.Among the 12 cases who took levodopa, 5 patients reduced their levodopa dosage after taking tolcapone additionally. There were 35 patients showing side-effects among 80 cases, and their degree was significantly severer in tolcapone group than in placebo group （ P 〈 0.01 ）, such as sleeplessness, nausea, vomiting, diarrhea, but no malignant accident occurred. Conclusion Talcapone could greatly improve PD patients＇ motor function, which could significantly reduce the ＂off＂ time in PD patients with motor fluctuations, and prolong the ＂on＂ time, which could also improve wearing-off phenomenon. Tolcapone is a safe and effective drug in treating patients with PD.