药品行政保护品种介绍:神经系统与精神药物(五)(续完)

神经妥乐平片剂通用名:牛痘免疫病毒疫苗接种家兔炎症皮肤组织提取物片剂.商品名:神经妥乐平(Neurotropin)片剂.     

Alzheimer’s disease treatment: Assessing caregiver preferences for mode of treatment delivery

Introduction  Management of patients with Alzheimer’s Disease (AD) can exert a substantial burden upon caregivers. As new modes of treatment administration are developed, it is important to assess caregiver satisfaction and preference in a standardized manner. This study describes the development of the Alzheimer’s Disease Caregiver Preference Questionnaire (ADCPQ) to assess AD caregivers’ satisfaction with and preference for patch or capsule treatments in AD patients. Methods  Twenty-five published articles (1987-2002) were reviewed to identify potential ADCPQ domains. Three caregiver focus groups (n=24) were conducted to develop a first draft of the questionnaire. After evaluating the acceptance of ADCPQ to caregivers through in-depth interviews (n=10), its psychometric properties were assessed using data from 986 patients enrolled in a multicenter, randomized, double-blind, four-arm, placebo- and active-controlled, 24-week trial. Results  Focus groups indicated that caregivers expressed dissatisfaction with current AD treatment routines including limitations related to: efficacy, administration schedule, number of pills, adherence to treatment, side effects, and taking pills. In-depth interviews with caregivers found the ADCPQ to be comprehensible with an acceptable layout. The resultant ADCPQ comprises three modules: A) baseline, 11 items assessing treatment expectations; B) week 8, 33 items on satisfaction and preferences with treatment options; C) week 24, 10 items assessing overall opinions of treatment options. Missing data per item was low (≤0.3%) and domain internal consistency reliability was good (0.71–0.91). Preference items were also valid when evaluating concordance and discordance between convenience and satisfaction patch and capsule domain scores. Conclusion  AD treatment puts a significant strain on caregivers. New modes of treatment delivery may be less burdensome to caregivers, thereby increasing satisfaction and potential treatment adherence. The ADCPQ was well accepted by AD caregivers and its domains demonstrated satisfactory psychometric properties. The ADCPQ is a useful tool to understand caregiver preferences for patch versus oral therapies in AD.     

HPLC法测定重酒石酸卡巴拉汀片含量

目的:建立HPLC法测定重酒石酸卡巴拉汀片中含量.方法:用C18色谱柱,以磷酸盐缓冲溶液(取磷酸二氢钠1.56 g和辛烷磺酸钠2.16 g,加水1000 mL溶解,用磷酸调pH值至4.0)-乙腈(70:30)为流动相,检测波长220 nm;流速为1 mL·min-1,柱温25℃.结果:卡巴拉汀在6.77～27.07μg·mL-1浓度范围内与其相应的峰面积呈良好的线性关系.回归方程为:Y=1 564.79X-2.862 54(r=0.999 8,n=13).精密度试验RSD为0.22%(n=6),平均回收率分别为100.0%,RSD为0.45%(n=9).结论:所建立的HPLC方法灵敏、准确、重现性好,操作简便,可有效测定重酒石酸卡巴拉汀片的含量.     

A pilot, randomized, open-label trial assessing safety and pharmakokinetic parameters of co-administration of rivastigmine with risperidone in dementia patients with behavioral disturbances

BACKGROUND: The majority of patients with Alzheimer's disease (AD) or vascular dementia display, in addition to cognitive impairment, various degrees of behavioral disturbances. As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread, many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances. Despite the widespread use of this combination in clinical practice, the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials. This pilot study examined the effects of addition of risperidone 0.5-2 mg/day to patients on rivastigmine 3-12 mg/day, and vice versa. METHODS: 65 patients suffering from AD, 10 from vascular dementia, and 15 from both were randomized to open label rivastigmine and risperidone, alone or in combination, for 20 weeks. Adverse events caused by co-administration were assessed. RESULTS: No clinically relevant adverse interactions were observed. CONCLUSIONS: These preliminary results indicate that rivastigmine and risperidone can be safely co-administered. Confirmation of these results in large clinical trials studies is warranted.     

多奈哌齐治疗轻中度阿尔茨海默病患者的临床研究

目的研究多奈哌齐治疗我国轻中度阿尔茨海默病(AD)患者的疗效和安全性.方法将48例轻中度AD患者随机均分为两组,用多奈吸哌齐和卡巴拉汀治疗16周.采用简易精神状态量表(MMSE)、Blessed-Roth量表和总体衰退量表(GDS)评定疗效.安全性检查包括生命体征,实验室及心电图检查,每4周1次.结果两组治疗前后MMSE,GDS和Blessed-Roth评分均有显著改善(P＜0.05).但两组治疗前后相关量表总分差值的t检验均无显著意义(P＞0.05).两组治疗前后Blessed-Roth各亚项分数差值比较无显著性(P＞0.05).不良反应为胃肠道反应,发生率在15.0%～29.5%之间,以卡巴拉汀组多见.结论多奈吸哌齐和卡巴拉汀可显著改善AD患者的认知功能、痴呆程度和日常生活能力,疗效相当,较为安全,耐受性较好.     

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease

BACKGROUND: Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. OBJECTIVE: To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. METHODS: We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. RESULTS: This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. CONCLUSION: Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.     

An open-label pilot study comparing rivastigmine and low-dose aspirin for the treatment of symptoms specific to patients with subcortical vascular dementia

Background: Patients with vascular dementia (VaD) show cholinergic deficits that may result in characteristic clinical syndromes for different subtypes of the condition. In addition to executive function, subcortical VaD is characterized by behavioral and emotional problems, reflecting deterioration of the frontal lobe.Objective: The purpose of this study was to determine the effect of rivastigmine on the specific symptoms of subcortical VaD.Methods: Patients received rivastigmine 3 to 6 mg/d (n = 8) or low-dose aspirin (cardioaspirin) 100 mg/d (n = 8) for 22 months in an open-label study design. Rivastigmine-treated patients began therapy with the lower dosage of rivastigmine 3 mg/d, which was increased to the higher dosage of 6 mg/d after 4 weeks. Disease severity was assessed using the Clinical Insight Rating Scale. Behavior was assessed using the NeuroPsychiatric Inventory (NPI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Cornell Scale for Depression in Dementia (CSDD). The main results of this study, including executive function, NPI, and caregiver stress scores, have been presented elsewhere.Results: Sixteen patients were enrolled. Patients receiving rivastigmine showed statistically significant improvements in their BEHAVE-AD and CSDD scores (P = 0.001 and P = 0.02, respectively, versus cardioaspirin). Comparison of individual items on the BEHAVE-AD scores of the rivastigmine group with the cardioaspirin group indicated statistically significant improvements in activity disturbance, affective disturbance, aggressiveness, anxiety/phobia, hallucinations, and paranoia/delusions (P = 0.007, P = 0.035, P = 0.008, P = 0.003, P = 0.006, and P = 0.001, respectively). Similarly, comparison of the NPI scores of the 2 groups showed that the rivastigmine group experienced significantly greater improvements in anxiety, hallucinations, and wandering (P = 0.001, P = 0.005, and P = 0.014, respectively). Side effects in both groups were tolerable and there were no study withdrawals.Conclusions: In this preliminary study, rivastigmine treatment was well tolerated and effective. Improvements in the symptoms that characterize subcortical VaD were observed, suggesting that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population. A large, double-blind, placebo-controlled study of rivastigmine in patients with VaD is warranted.     

卡巴拉汀脂质体的制备及其大鼠鼻腔给药的药代动力学

制备卡巴拉汀脂质体,研究其在大鼠鼻腔给药的药代动力学。采用硫酸铵梯度法制备包载卡巴拉汀的脂质体,考察粒径、zeta电位和包封率,测定脂质体在磷酸盐缓冲液中的释放;大鼠鼻腔给予卡巴拉汀脂质体,以安替比林为内标,采用高效液相色谱-串联质谱法(HPLC/MS)测定血浆中卡巴拉汀的浓度,运用DAS 2.0软件拟合药代动力学参数。经筛选制备的脂质体包封率为(33.41±6.58)%,平均粒径在154～236 nm,zeta电位(-10.47±2.41)mV。脂质体的体外释放符合一级动力学方程。大鼠鼻腔给药后,Cmax,Tmax和AUC0-∞分别为(1.50±0.15)mg.L-1,15 min和(89.06±8.30)mg.L-1.min。卡巴拉汀制备成脂质体经大鼠鼻腔给药后,吸收迅速,血药浓度可以达到一定水平。     

Cholinesterase inhibitors in dementia with Lewy bodies: a comparative analysis

OBJECTIVE: To compare efficacy of different cholinesterase inhibitors (ChEIs) for treating patients with dementia with Lewy bodies (DLB). DESIGN: Retrospective comparison of three independent clinical studies of ChEI treatment using donepezil, galantamine or rivastigmine in patients with DLB. METHOD: Data was obtained from open label trials of donepezil and galantamine and a placebo controlled randomized trial of rivastigmine in DLB. Changes in Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and United Parkinson's Disease Rating Scale (UPDRS-III) scores were compared between the three treatments at 12 and 20 weeks. RESULTS: All ChEIs significantly improved cognitive and neuropsychiatric measures. Reduction in the total NPI score appeared significantly greater after donepezil treatment. There was no significant increase in UPDRS-III scores. CONCLUSIONS: It is unclear to what extent these findings reflect true differences between ChEIs or are due to methodological artefacts of comparing different studies. There is so far no compelling evidence that any one ChEI is better than the other in treating DLB but head to head comparative studies of different ChEIs are warranted to clarify this.