美金刚与多奈哌齐合用对帕金森痴呆患者MoCA、ADL与血清CRP、PARK7的影响

【摘要】 目的 研究分析美金刚与多奈哌齐合用对帕金森痴呆患者MoCA、ADL与血清CRP、PARK7的影响。方法 选取本院收治的89例行帕金森痴呆患者进行研究,将所选患者按照治疗方法的不同随机分为研究组49例与对照组40例。对照组患者给予多奈哌齐进行治疗,研究组在对照组基础上联合美金刚进行治疗。回顾性分析两组患者的临床资料,对比分析两组患者临床疗效、认知功能以及日常生活能力的具体情况,并记录治疗期间不良反应发生情况。结果 对照组总有效率为7750%,研究组总有效率为9592%,研究组总有效率高于对照组（P＜005）;治疗12周后,两组患者UPDRS总评分、MMSE评分、MoCA评分、ADL评分均较前明显改善。研究组UPDRS总评分低于对照组,MMSE评分、MoCA评分、ADL评分高于对照组,两组对比存在明显差异（P＜005）;治疗12周后,两组患者血清CRP、PARK7、NT 3水平均较前明显改善。研究组血清CRP、PARK7水平低于对照组,NT 3水平高于对照组,两组对比存在明显差异（P＜005）;对照组患者治疗后的不良反应发生率（1250%）高于研究组患者（1224%）,但两组比较无明显差异（P＞005）。结论 美金刚与多奈哌齐合用对帕金森痴呆患者具有良好的临床疗效,可以有效改善帕金森痴呆患者行为功能以及认知功能,并明显降低患者血清CRP、PARK7水平,提高了NT 3水平,且安全性较高,可作为帕金森痴呆患者首选的治疗方案。     

葛根素注射液联合多奈哌齐治疗帕金森病的疗效观察

目的探讨葛根素注射液联合盐酸多奈哌齐片治疗帕金森病的临床疗效。方法选取2016年2月—2017年12月南阳市中心医院收治的帕金森病患者98例为研究对象,所有患者随机分为对照组和治疗组,每组各49例。对照组患者睡前口服盐酸多奈哌齐片,1片/次,1次/d,维持1个月,然后根据治疗效果增加剂量至2片/次,1片/d。治疗组在对照组基础上静脉滴注葛根素注射液,400 mg加入到5%葡萄糖溶液500 m L中,1次/d。15 d为1个疗程,两组患者连续治疗3个疗程。观察两组的临床疗效,比较两组的改良Webster症状评分。结果治疗后,对照组和治疗组的总有效率分别为79.59%、91.83%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者改良Webster症状评分均显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组患者改良Webster症状评分显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论葛根素注射液联合盐酸多奈哌齐片治疗帕金森病具有较好的临床疗效,可改善临床症状,安全性较好,具有一定的临床推广应用价值。     

丹红注射液联合多奈哌齐治疗阿尔茨海默病的临床研究

目的探讨应用丹红注射液联合多奈哌齐治疗阿尔茨海默病的临床效果。方法选取2015年6月—2017年6月中国人民解放军白求恩国际和平医院收治的阿尔茨海默病患者106例,随机分成对照组(53例)与治疗组(53例)。对照组睡前口服盐酸多奈哌齐片,5 mg/次,1次/d。治疗组在对照组基础上静脉滴注丹红注射液,40 m L加入250 m L生理盐水,1次/d。两组均连续治疗4周。评价两组患者临床疗效,同时比较治疗前后两组患者简易精神状态量表(MMSE)评分、脑血流动力学和血清学指标。结果治疗后,对照组临床有效率为77.4%,显著低于治疗组的92.5%,两组比较差异具有统计学意义(P0.05)。治疗后,两组MMSE评分较治疗前均显著增加(P0.05);且治疗组比对照组升高更显著(P0.05)。治疗后,治疗组基底动脉(BA)和双侧大脑中动脉(MCA)的平均血流速度(MFV)值均显著升高(P0.05),搏动指数(PI)值显著下降(P0.05);且治疗后治疗组BA和双侧MCA的MFV值和PI值比对照组改善更显著(P0.05)。治疗后,两组血清血清磷酸化tau蛋白(P-tau)、丙二醛(MDA)、白细胞介素(IL)-8和超敏C反应蛋白(hs-CRP)水平较治疗前均显著降低(P0.05),超氧化物歧化酶(SOD)水平均显著增加(P0.05);且治疗组上述血清学指标比对照组改善更显著(P0.05)。结论应用丹红注射液联合多奈哌齐治疗阿尔茨海默病可有效改善患者脑血流状态,减轻机体氧化应激与炎症损伤,提高认知功能,延缓病情进展。     

盐酸多奈哌齐口崩片的处方优选及稳定性研究

目的:优选盐酸多奈哌齐口崩片处方并考察其稳定性。方法:采用正交试验确定最佳处方,并与普通薄膜衣片进行体外溶出度比较。在不同条件下留样进行稳定性研究。结果:筛选后最佳处方为崩解剂用量10%、填充剂用量20%、泡腾剂用量5%,所制制剂崩解迅速,几乎在30s内崩解完全,并能通过内径为710μm的筛,其溶出速度快于普通片剂,稳定性均合格。结论:所得口崩片质量稳定,有效期定为2y。     

A Randomized,Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States

To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period crossover studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment arms (test or reference) separated by a washout period of 28 days. Blood samples were collected up to 72 h post-dose and plasma samples were analyzed for donepezil using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI of C_max and AUC_0-72 were 82.50–90.10 and 92.38–98.60, respectively. Corresponding values in the fed study were 91.82–98.05 and 97.27–100.27. Based on the results, the test product (donepezil) met the US regulatory criteria of bioequivalence relative to the reference product (Aricept^®) under both fasting and fed conditions.     

多奈哌齐联合丁苯酞软胶囊治疗血管性痴呆临床观察

目的 观察多奈哌齐联合丁苯酞软胶囊对血管性痴呆（VD）患者的治疗作用.方法 VD患者60例,随机分为联合治疗组、多奈哌齐组各30例.联合治疗组给予丁苯酞软胶囊与多奈哌齐联合治疗,多奈哌齐组仅给予多奈哌齐.2组患者分别在治疗前及治疗8周、12周后进行蒙特利尔认知（MoCA）量表测评.结果 治疗8周、12周后,联合治疗组的MoCA评分及视空间与执行功能、注意力、延迟回忆、定向力等子项目的 改善优于多奈哌齐组（P＜0.05）.结论 多奈哌齐联合丁苯酞软胶囊对血管性痴呆患者的认知功能有较好的改善作用,且对MoCA评分各主要子项目都有较好的改善作用.     

An open-label,comparative study of rivastigmine,donepezil and galantamine in a real-world setting

SUMMARY

Objective:We analysed the effects of donepezil, rivastigmine and galantamine, prescribed for the treatment of Alzheimer disease in a real-world setting in Italy.

Methods: Outcome measures included the Mini-Mental State Examination (MMSE), the Alzheimer Disease Assessment Scale cognitive subscale (ADAS-cog), Instrumental Activity of Daily Living (IADL) and ADL scales.

Results: Seventy patients were treated with donepezil, 121 with rivastigmine and 51 with galantamine. At 6 months, rivastigmine-treated patients improved by 1.29 points from baseline on the ADAS-cog, while donepezil- and galantamine-treated patients showed 'no change' (changes of < 0.2 points). On the IADL, patients treated with rivastigmine, donepezil and galantamine showed decreases of 0.42,0.58 and 0.75 points, respectively. On the ADL, donepezil- and galantamine-treated patients showed decreases of 0.44 and 0.86 points, respectively, while there was 'no change' with rivastigmine. On the MMSE,

donepezil- and rivastigmine-treated patients showed 'no change' and galantamine-treated patients showed a mean decrease of 1.19 points. A subgroup analysis of 'pseudo-randomised' patients (rivastigmine, n?=?63; donepezil, n?=?55; galantamine, n?=?51) supported the main findings. Side effects were similar (in type and frequency) in the three treatment groups.

Conclusions: This is the first study to compare the effects of the three most commonly-used cholinesterase inhibitors on the MMSE, ADAS-cog, IADL and ADL. Limitations included its small population size, its open-label design, and the fact that patients were randomised only after the introduction of galantamine. There were no statistically significant differences between the three drugs at 3 months. While numerical trends were observed suggesting the effect of rivastigmine > donepezil > galantamine, larger, longer-term prospective studies are needed to confirm whether there are important differences in the long-term efficacy of the three drugs.     

Efficacy and Safety of Rivastigmine in Patients with Alzheimer's Disease who Failed to Benefit from Treatment with Donepezil

Summary

Background: Selective acetylcholinesterase (AChE) and dual acetyl- and butyrylcholinesterase inhibitors constitute the only approved agents for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is a specific, reversible inhibitor of AChE, while rivastigmine is a slowly reversible (pseudoirreversible) dual cholinesterase (ChE) inhibitor, with brain-regional specificity for the cerebral cortex and hippocampus. According to the European Marketing Authorisations, the clinical benefit of ChE inhibitors should be reassessed on a regular basis and discontinuation should be considered when evidence of a therapeutic effect is no longer present. However, substantial differences in the pharmacological and pharmacokinetic profiles of the available ChE inhibitors suggest that it may be desirable to switch between ChE inhibitors if patients fail to show efficacy, deteriorate or are unable to tolerate their initially prescribed medication.

Design: This open-label, six-month study evaluated the efficacy and safety of rivastigmine in 382 AD patients who had previously failed to benefit from treatment with donepezil (80% due to lack of efficacy, 11% due to tolerability problems, 9% both reasons).

Results: At the end of the study, 56.2% of patients were responders to rivastigmine, as assessed using a global function scale (the Clinicians’ Global Impression of Change). Cognitive performance (measured by the Mini-Mental State Examination) and the ability to perform activities of daily living (measured by the Instrumental Activities of Daily Living scale) were improved/stabilised in 48.9% and 57.0% of patients, respectively. Rivastigmine was generally well tolerated, the most common adverse events being nausea and vomiting, consistent with reports from previous clinical studies. The occurrence of side-effects or lack of efficacy with donepezil treatment was not a predictor of similar problems when treated with rivastigmine.

Conclusion: Rivastigmine treatment appears to be beneficial in AD patients who have previously failed to benefit from, or were unable to tolerate treatment with, donepezil.     

Impact of donepezil treatment for Alzheimer's disease on caregiver time

SUMMARY

Objective: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD).

Research design and methods: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0?h/day reported on the RUD) providing care at study baseline.

Main outcome measures: The change in time relative to baseline that caregivers spent assisting patients over the course of the study.

Results: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52?weeks, caregivers of placebo patients were providing almost 2?h each day (106.8?min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6?min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1?h (64.2?min) each day, and was significant (?p = 0.03).

Conclusion: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.     

多奈哌齐对颅脑外伤后患者认知功能障碍的疗效观察

摘 要 目的:观察多奈哌齐对颅脑外伤后患者认知功能障碍的改善作用。方法：颅脑外伤后认知功能障碍住院患者76例随机分为观察组和对照组各38例。两组患者均予控制颅内压、神经营养及防治并发症等基础治疗。观察组患者加用多奈哌齐片5 mg,po qd;对照组患者加用脑复康片1.2 g,po tid。两组均连用2周。观察两组患者治疗前后认知功能指标的变化,比较两组疗效及药品不良反应。结果：治疗2周后,两组患者WMS评分和MOCA评分均较前明显上升(P＜0.05或P＜0.01),且观察组较对照组上升更明显(P＜0.05);观察组患者认知功能总改善率为94.74%,明显高于对照组的76.32%(P＜0.05)。两组药品不良反应发生率比较,差异无统计学意义(P＞0.05)。结论：多奈哌齐对颅脑外伤后患者认知功能障碍具有良好的改善作用,能促进患者认知功能的恢复,且安全性较好。