恩他卡朋双多巴联合B族维生素治疗中晚期帕金森病临床分析

目的探讨恩他卡朋双多巴联合B族维生素对中晚期帕金森患者的临床疗效。方法收集中晚期帕金森病(PD)患者80例,将其随机分为美多芭组、美多芭+B族维生素组、达灵复组、达灵复+B族维生素组,治疗6个月后评估LD血药浓度、UPDRSⅢ评分、H-Y分级、PSQI、PDQ-39等指标。结果与治疗前相比,达灵复+B族维生素组能显著降低血浆Hcy水平以及PSQI、PDQ-39、UPDRSⅢ评分(P0.05),提高LD血药浓度(P0.05);与美多芭+B族维生素组相比,达灵复+B族维生素组可提高LD血药浓度(P0.05),降低血浆Hcy水平(P0.05)。结论达灵复联合B族维生素可提高中晚期PD患者LD血药浓度,降低血浆Hcy水平,改善临床症状和生活质量。     

恩他卡朋添加治疗对药效减退的帕金森病患者的疗效观察

目的 探讨恩他卡朋添加治疗对药效减退的帕金森病(PD)患者的疗效及安全性.方法 对4l例服用美多芭疗效减退的PD患者添加恩他卡朋治疗.在添加恩他卡朋治疗前和治疗后第1个月、2个月、3个月分别进行"统一PD评定量表(UPDRS)"评分及运动诱发电位(MEP)检查,比较各时间点美多芭的每日服用总量,并观察其不良反应.结果 添加恩他卡朋治疗后第1个月、2个月、3个月UPDRSⅡ和UPDRSⅢ评分均较添加治疗前明显下降,差异有统计学意义(均P＜0.05),美多芭每日服用总量也明显减少,与添加治疗前比较有统计学意义(均P＜0.05);MEP静息阈值(RMT)在治疗后第3个月明显升高(P＜0.05),潜伏期(CL)及皮质静息期(CSP)明显延长(均P＜0.05);无严重不良反应.结论 恩他卡朋添加治疗能有效改善美多芭药效减退PD患者的运动功能,且安全.     

美多芭对帕金森病患者抗氧化效应的研究

目的探讨左旋多巴血药浓度与帕金森病(PD)患者治疗效果的相关性。方法选择81例临床确诊为原发性PD的患者,其中68例为服用美多芭的患者(给药组),13例为未服用药物的患者(未给药组),对比美多芭治疗后外周血中左旋多巴的水平及统一PD评分量表(UPDRSⅢ)的评分;检测患者血浆谷胱甘肽(GSH)、GSH过氧化物酶(GSH-Px、活性氧(ROS)水平,并与健康者(对照组)比较。结果给药组左旋多巴血药浓度为(2.189±1.065)μg/ml,给药组服药前后UPDRSⅢ的评分均显著低于对照组(P0.05~0.01)。与未给药组相比,给药组血浆中的GSH、GSH-PX水平明显上升(均P0.05)。给药组中对机体氧化损伤影响较大的为患病病程。结论美多芭能通过清除自由基显著改善PD患者的症状。     

左旋多巴联合恩他卡朋治疗帕金森病疗效观察

目的研究左旋多巴联合恩他卡朋治疗帕金森病(PD)的疗效及对炎症因子、氧化应激指标水平的影响。方法选取132例PD患者为研究对象,随机数字表法分成治疗组和对照组各66例。治疗组给予左旋多巴联合恩他卡朋治疗,对照组给予左旋多巴治疗。3个月后采用帕金森统一评分量表(UPDRS)比较2组临床疗效,记录其治疗前后血清炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]、血浆氧化应激指标[超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)水平变化情况。结果 2组治疗后UPDRS评分和IL-1β、IL-6、MDA水平均较治疗前显著降低(P0.05),SOD、GSH水平则较治疗前显著升高(P0.05),且治疗组变化幅度大于对照组(P0.05);治疗组总有效率优于对照组(P0.05)。结论左旋多巴联合恩他卡朋方案对PD患者体内炎症因子和氧化应激指标水平有一定调节作用,疗效确切,于病情转归有利。     

美多芭联合多巴胺受体激动剂治疗帕金森病的临床疗效

目的评价美多芭联合多巴胺受体激动剂治疗帕金森病的临床疗效。方法选取我院收治的帕金森病患者108例,随机分为观察组55例,采用美多芭联合多巴胺受体激动剂治疗,对照组53例,仅采用美多芭治疗,观察并比较2组临床疗效及帕金森综合评分量表(UPDRS)评分。结果观察组临床疗效明显优于对照组,差异有统计学意义(P0.05);观察组治疗后UPDRSⅡ(日常活动)、UPDRSⅢ(运动功能)、UPDRSⅣ(治疗并发症)均明显低于对照组,差异均有统计学意义(P0.05)。结论美多芭联合多巴胺受体激动剂治疗帕金森病的临床疗效好,可有效提高患者日常活动及运动功能,降低并发症,值得临床推广。     

同型半胱氨酸在帕金森病患者血浆中的变化及临床意义

目的对比研究同型半胱氨酸(homocystein,Hcy)在帕金森病(Parkinson’s disease,PD)和脑梗死患者血浆中的变化,探讨其临床意义。方法检测PD、脑梗死患者及对照组血浆Hcy水平,检测PD、脑梗死患者及对照组血浆叶酸和维生素B_(12)水平。对PD患者血浆Hcy水平与叶酸及维生素B_(12)水平进行相关性分析,对血浆Hcy水平与PD严重程度、病程、临床类型、情绪、认知功能及是否服用美多芭进行相关性分析。结果 (1)PD组、脑梗死组及对照组血浆Hcy水平分别为20±11μmol/L、16±7μmol/L及11±2μmol/L,PD组和脑梗死组血浆Hcy水平均高于对照组,差异有统计学意义(P0.05或0.01),PD组血浆Hcy水平明显高于脑梗死组(P0.01);(2)PD组血浆叶酸和维生素B_(12)水平分别为6±5μg/L和514±345ng/L。PD组血浆叶酸和Hcy水平呈明显负相关(r=-0.453,P0.01);血浆维生素B_(12)和Hcy水平无明显相关性(r=-0.268,P0.05)。(3)按照Hoehn-Yahr分期对PD严重程度进行分组,轻、中、重度PD组血浆Hcy水平分别为16±8μmol/L、21±9μmol/L和35±3μmol/L,三组之间差异有统计学意义(P0.05);(4)血浆Hcy水平与病程、临床类型、情绪、认知功能及是否服用美多芭无关。结论 PD组和脑梗死组血浆Hcy水平明显增高,PD组Hcy水平与疾病严重程度密切相关,PD组血浆叶酸和Hcy水平呈明显负相关。     

参附注射液对帕金森病临床疗效的影响

目的研究联用参附注射液对帕金森病(PD)的临床疗效及血清炎性因子水平的影响。方法选取PD患者40例,随机分为对照组(19例)和观察组(21例)。入院后对照组给予美多芭治疗,观察组联合使用参附注射液治疗。比较两组的统一PD评定量表(UPDRS)、PD睡眠量表(PDSS)、汉密尔顿抑郁量表(HAMD)、MMSE评分。同时对比两组血清IL-1β、IL-6、TNF-α、核转录因子(NF-κB)-p65水平变化。结果观察组患者治疗后UPDRSⅡ、UPDRSⅢ及总UPDRS评分明显低于治疗前及对照组,差异有统计学意义(均P0.05)。观察组患者治疗后HAMD明显低于治疗前及对照组,差异有统计学意义(均P0.05);而PDSS、MMSE结果差异无统计学意义(均P0.05)。对照组和观察组各项炎症因子水平均显著高于健康组,差异有统计学意义(均P0.01)。观察组患者治疗后IL-1β、IL-6水平明显低于治疗前及对照组,差异有统计学意义(均P0.01);而观察组与对照组患者治疗前后TNF-α、NF-κB-p65结果差异无统计学意义(均P0.05)。结论联合使用参附注射液可以明显改善PD患者的多项评分结果和炎症因子水平,对PD治疗有积极作用。     

美多芭联合tDCS治疗PD的疗效及对UPDRS评分的影响分析

目的探讨美多芭联合经颅直流电刺激(t DCS)治疗帕金森(PD)的疗效及对PD综合评分量表(UPDRS)评分的影响。方法将本院2016年3月至2017年3月期间收治的94例PD患者根据随机数字法分为试验组和对照组,试验组给予美多芭联合t DCS治疗,对照组给予美多芭治疗,分别于治疗前、治疗后7d及1个月对UPDRS评分、治疗效果以及不良反应等进行综合评价。结果治疗1个月后,试验组患者的治疗总有效率为82.98%显著高于对照组的72.34%,组间比较差异有统计学意义(P0.05)。对照组失眠2例,便秘2例,头晕3例,体位性低血压2例,不良反应发生率为23.40%。试验组失眠4例,便秘1例,头晕5例,体位性低血压1例,不良反应发生率为19.15%,两组的不良反应发生率(P0.05);治疗7d及1个月后,试验组UPDRSⅠ、Ⅱ、Ⅲ及总的评分均低于对照组,组间差异有统计学意义(P0.05)。结论对PD患者采用美多芭联合t DCS治疗方案,能显著改善患者的UPDRS评分,且该法具有较高的临床安全性,今后可能成为有潜力的PD治疗方法。     

不同药物对帕金森病患者血浆同型半胱氨酸的影响

目的探讨不同药物治疗方法对帕金森病患者血浆同型半胱氨酸(Hcy)、叶酸、维生素B12的影响,以及PD患者病情程度与血浆Hcy的关系。方法 79例PD患者按服药不同分为4组,比较各组血浆Hcy水平;观察Hoehn-Yahr(H-Y)分期与血浆Hcy水平的关系;观察血浆Hcy水平与病程的关系;观察不同治疗组患者叶酸、维生素B_(12)含量。结果服多巴胺制剂组血浆Hcy水平明显高于未服药组(P0.05);Hcy水平较高者H-Y分期较高(P0.05);病程较长的患者血浆Hcy水平升高(P0.05);服多巴胺制剂组患者叶酸、维生素B12水平均较未服药组明显降低(P0.05)。结论多巴胺制剂可引起血浆Hcy水平升高,使叶酸、维生素B12水平降低,有可能促进PD进展;血浆Hcy水平高者运动障碍分期较高,病程较长,即病情相对较重。     

恩他卡朋治疗帕金森病剂末现象的临床观察

目的探讨恩他卡朋对PD患者剂末现象影响。方法选择40例出现剂末现象的PD患者进行相关资料分析,根据不同治疗方案分为普拉克索组和恩他卡朋组,入选患者治疗8周,分析恩他卡朋对PD剂末现象的疗效。结果恩他卡朋组疗效(90%)高于普拉克索组(60%),UPDRSⅡ评分低于普拉克索组,关期时间短于普拉克索组;恩他卡朋组异动症时间(2.3±0.6)h,低于普拉克索组的(2.7±1.0)h,差异均有统计学意义(P0.05)。结论恩他卡朋能够延长患者开期时间,缩短关期时间,改善剂末现象开期运动症状。     

Long-term comparative experience with tolcapone and entacapone in advanced Parkinson's disease

The objective of this study was to compare the long-term tolerability and efficacy of tolcapone and entacapone in patients with fluctuating Parkinson's disease (PD). Tolcapone and entacapone are two currently available catechol- O -methyltransferase inhibitors that have demonstrated efficacy in the treatment of advanced PD. There are little published data on long-term experience and no direct comparisons. We compared the results of two separate, simultaneous, long-term open label extensions, one for tolcapone and the other for entacapone. The inclusion/exclusion criteria were similar. Data were collected prospectively at 6, 12, 24, and 36 months. Efficacy measures included the Unified Parkinson's Disease Rating Scale (UPDRS) total score, subscores, items 32 (duration of dyskinesia) and 39 (duration of "off" time), and levodopa dose. The two groups were compared using a Mann-Whitney U test for change from baseline and analysis of variance. Tolerability was defined as the ability of patients to maintain therapy and was compared using a Kaplan-Meier analysis. Eleven patients enrolled in the entacapone study and 14 in the tolcapone study. The tolcapone group had more severe disease with significantly higher UPDRS motor score, duration of "off," and levodopa dose requirement. Tolcapone was more effective in lowering UPDRS motor and complication subscores, duration of "off" time, and levodopa doses. UPDRS motor scores and change in levodopa dose in the tolcapone group remained below baseline level for 36 months; however, they were above baseline in the entacapone group from 6 months on. Tolerability was the same for both treatments. Tolcapone appears to have greater and longer efficacy with regard to motor symptoms, "off" time, and change in levodopa requirements than entacapone. These findings indicate that tolcapone continues to have a place in the treatment of advanced PD. However, the risks associated with this drug, particularly hepatic injury, and the requirement for rigorous blood monitoring, need to be considered when choosing an appropriate treatment for patients with advanced PD.     

Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study)

OBJECTIVES: To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone, used as an adjunct to levodopa, in Parkinson's disease (PD) patients. PATIENTS AND METHODS: In this parallel group, randomized, double-blind study, 301 PD patients, the majority with motor fluctuations, received entacapone (200 mg) or placebo with each daily dose of standard or controlled-release (CR) levodopa. The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off' times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. RESULTS: In the total population, the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off' time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively; P < 0.05), and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). Entacapone benefit was lost on withdrawal. Entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. CONCLUSION: Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.     

Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone

We aimed to investigate whether treatment with levodopa/carbidopa/entacapone when compared with levodopa/carbidopa improves quality of life in Parkinson's disease (PD) patients with no or minimal, nondisabling motor fluctuations. This is a multicenter, randomized, double‐blind study. One hundred eighty‐four patients on 3 to 4 equal doses of 100/25 to 200/50 mg levodopa/carbidopa or levodopa/benserazide, 0 to 3 hours of nondisabling OFF time over a 48 hour period and no dyskinesia were randomized to levodopa/carbidopa/entacapone or levodopa/carbidopa treatment for 12 weeks. The primary outcome measure was quality of life as assessed by the PDQ‐8. Secondary outcome measures were the UPDRS parts I–IV, and the Wearing Off Card. Treatment with levodopa/carbidopa/entacapone resulted in significantly greater improvements in PDQ‐8 scores compared to treatment with levodopa/carbidopa (mean difference 1.4 points, P = 0.021). Statistically significant improvements were seen predominantly in nonmotor domains (depression, personal relationships, communication, stigma, all P < 0.05; dressing P = 0.056). Patients who were randomly assigned to levodopa/carbidopa/entacapone also showed significantly greater improvement in UPDRS part II scores (P = 0.032) with UPDRS part III scores showing borderline significance. Differences in UPDRS parts I and IV and Wearing Off Card scores were not significant. Treatment with levodopa/carbidopa/entacapone results in improved quality of life compared with levodopa/carbidopa in PD patients with mild or minimal, nondisabling motor fluctuations. © 2007 Movement Disorder Society     

Efficacy of combining levodopa with entacapone on quality of life and activities of daily living in patients experiencing wearing-off type fluctuations

OBJECTIVES: To compare the efficacy of levodopa/dopa decarboxylase inhibitor (DDCI) plus entacapone with levodopa/DDCI plus placebo on measures of parkinsonian disability and health-related quality of life (QoL) in subjects with Parkinson's disease (PD) experiencing motor fluctuations. MATERIALS AND METHODS: A double-blind, placebo-controlled phase IV study was performed in 270 PD patients randomized to receive either entacapone 200 mg or placebo with each dose of their current levodopa regimen. The primary variables were the Unified Parkinson's Disease Rating Scale (UPDRS) part II activities of daily living (ADL) and the Parkinson's Disease Questionnaire (PDQ)-39 summary index. UPDRS parts I, III-VI, Global Assessment of Change, PDQ-39 subscores, and the Short-Form (SF)-36 and the European Quality of Life five-dimension questionnaire (EQ-5D) were included as secondary variables. RESULTS: There was a significant improvement in ADL scores with levodopa/DDCI/entacapone compared with levodopa/DDCI/placebo at 5 and 13 weeks (-2.3 vs -0.7, respectively; P = 0.0001). However, no significant differences were observed between treatments using the PDQ-39 summary index. UPDRS part III (motor) scores significantly decreased in the levodopa/DDCI/entacapone group compared with the levodopa/DDCI/placebo group (-5.0 vs -2.9, respectively; P = 0.03). Similarly, the change in the investigators Global Assessment was significantly greater (P = 0.004) in the levodopa/DDCI/entacapone group. There were no significant differences between treatments for any of the PDQ-39 subscores, the SF-36 variables or the EQ-5D utility score. CONCLUSIONS: Levodopa combined with entacapone demonstrated good efficacy in terms of ADL, global function, motor performance and was well tolerated. However, this short-term study did not generate significant improvements in QoL.     

交叉电脉冲在帕金森病DBS后程控中的应用

目的 探讨交叉电脉冲（ILS）在帕金森病（PD）脑深部电刺激术（DBS）后传统刺激方式疗效不佳病人中的应用效果。方法 回顾性分析2018年2月至2021年10月丘脑底核（STN）-DBS治疗的12例PD的临床资料。12例DBS后应用传统刺激方式疗效不佳,使用ILS（时间>6个月）。使用ILS后随访6~12个月,采用统一帕金森病生活量表（UPDRS Ⅱ）评分、运动量表（UPDRS Ⅲ）评分、异动症量表（UPDRS Ⅳ-A）评分评估疗效及左旋多巴等效日剂量（LEDD）评价药物使用情况。结果 与ILS前（药物关期）相比,使用ILS后（药物关期）UPDRS-Ⅱ评分、UPDRS Ⅳ-A评分、UPDRS-Ⅲ评分总分均明显改善（P<0.05）,LEDD无明显变化（P>0.05）。结论 PD病人STN-DBS后,在传统刺激模式症状改善不佳或出现刺激副反应时,ILS可明显改善PD症状、减轻刺激相关副反应。     

Effects of vitamin B12, folate,and entacapone on homocysteine levels in levodopa-treated Parkinson’s disease patients: A randomized controlled study

IntroductionPrevious studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson’s disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients.MethodsWe analyzed and compared plasma Hcy levels in 20 levodopa-naïve PD patients and 42 levodopa-treated PD patients, followed by randomized assignment of 42 levodopa-treated patients to treatment groups with either vitamin B12 and folate, entacapone, or no medication.ResultsPlasma Hcy levels in levodopa-treated PD patients were higher than those in the control group, but the difference was not statistical significant (15.25 ± 6.70 and 13.13 ± 4.68, P = 0.216). Patients treated with vitamin B12 and folate had a significant decrease in plasma Hcy levels (P < 0.001). In the entacapone group, Hcy levels were mildly decreased, but the change did not reach statistical significance.ConclusionLevodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. Unlike entacapone, combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma Hcy. We suggest that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated patients.     

Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.     

Efficacy and safety of levodopa with entacapone in Parkinson's disease patients suboptimally controlled with levodopa alone, in daily clinical practice: an international, multicentre, open-label study

The combination of entacapone with levodopa is effective in the treatment of Parkinson's disease (PD), providing significant improvements in 'on' time and Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL scores in controlled clinical trials. This multicentre, open-label study was designed to further evaluate the effectiveness of levodopa combined with entacapone 200 mg in routine clinical practice. Patients experiencing end-of-dose wearing-off were treated for 8 weeks (treatment phase), with an optional extension phase up to 20 weeks. The primary efficacy parameter was the Investigators' Global Assessment of Change; secondary efficacy parameters included UPDRS, 'off' time (from patient diaries), Patients' Global Assessment of Change, quality of life (QoL), SF-36 Health Assessment Questionnaire and Parkinson's Disease Questionnaire 39 (PDQ-39). Of the 479 patients who entered this study, 427 (89.1%) completed the treatment phase and 374 (78.1%) continued into the extension phase. Based on the Investigators' Assessment of Change, 380 (79.7%) patients showed an improvement with entacapone during the treatment phase. This improvement was maintained into the extension phase, and at Week 20, 301 (82.2%) patients continued to show an improvement. A positive treatment effect with entacapone was also seen with all secondary efficacy parameters, including QoL. Mean change in the total PDQ-39 scores showed improvements from baseline of -4.0 score points to the end of the treatment phase (n=182) and -3.1 score points at the end of the extension phase (n=152). Entacapone in combination with levodopa was generally well tolerated: 40 patients (8.4%) discontinued treatment due to adverse events (AEs) by the end of the extension phase. This study in a daily clinical practice setting confirmed the efficacy of coadministering entacapone with levodopa shown in controlled clinical trials and suggests that the combination is useful in improving the disability and QoL in patients with PD.     

Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized,double-blind,multicentre study

The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinson's disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations. Patients were randomized in a 3 : 2 ratio to entacapone 200 mg or placebo, administered with each dose of levodopa. Efficacy was judged on the improvement of "on" and "off" time while awake (Patient Diary and UPDRS part IV Item 39), Investigators' Global Assessment, the SF-36 Health Survey, and changes in levodopa dosages. Patients were monitored for adverse events, laboratory safety and vital signs throughout the study. Improvements in "on" time as assessed using patient diary data showed a trend in favour of entacapone, however these did not reach statistical significance. "Off" time while awake (UPDRS part IV Item 39) showed an improvement of at least one category in 36% of entacapone-treated patients, compared with 22% in the control group (p = 0.0038). The proportion of patients showing an improvement at the Investigators' Global Assessment was significantly higher (p = 0.0006) in the entacapone-treated group of patients. Also, the proportion of patients with a reduction in their daily levodopa dose was significantly higher (p = 0.02) in the entacapone group (28%) compared with placebo (13%). As expected, the most frequent adverse events were dopamine-mediated (dyskinesia: entacapone 31% versus placebo 13%), and harmless urinary discoloration. The modest increase in dyskinesias could be readily managed by levodopa down-adjustment, and, at study end there was no significant difference for the UPDRS "overall dyskinesia score" between entacapone and placebo. In conclusion, although the primary efficacy variable did not reach statistical significance, the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy.     

Optimizing levodopa therapy for Parkinson's disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective

After 40 years of clinical experience, levodopa remains the gold standard treatment for Parkinson's disease (PD) despite the recent emergence of a host of new therapies. Some physicians are cautious when prescribing levodopa because of its association with motor complications. Evidence now suggests that levodopa-associated complications are a result of deep troughs in delivery of levodopa to the brain caused by the short plasma half-life of conventional levodopa formulations (levodopa and a dopa decarboxylase inhibitor [DDCI]). Dosing strategies, such as dose increases and dose fractionation, may be effective in the short term. For the longer-term, levodopa/carbidopa/entacapone provides pharmacokinetically optimized levodopa therapy that significantly increases the plasma half-life and bioavailability of levodopa, providing more consistent plasma levodopa levels without deep troughs. Evidence from clinical trials in PD patients experiencing re-emergence of symptoms due to wearing-off has consistently shown that levodopa/DDCI and entacapone significantly increases ON-time and affords greater functionality, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) with conventional levodopa. These trials have also shown that levodopa/DDCI and entacapone is generally well tolerated, with notable adverse events including worsening dyskinesia, nausea and diarrhea. Patients experiencing re-emergence of symptoms due to wearing-off may benefit from optimized levodopa therapy with levodopa/carbidopa/entacapone.