RP-HPLC法测定人血浆中帕利哌酮的浓度

目的:建立测定人血浆中帕利哌酮浓度的方法。方法:血样以乙醚处理后采用反相高效液相色谱法进样测定。色谱柱为Agilent Eclipse Plus C18,流动相为甲醇-乙腈-水(1∶5∶14,加入1.88%正丁胺以及1.80%冰醋酸),流速为1.0 ml/min,检测波长为280nm,温度为室温(18²8℃),内标为曲唑酮,湿度<85%。结果:帕利哌酮血药浓度在2.8128℃),内标为曲唑酮,湿度<85%。结果:帕利哌酮血药浓度在2.81¹80 ng/ml范围内线性关系良好(r=0.999 0);平均方法回收率在99.01%180 ng/ml范围内线性关系良好(r=0.999 0);平均方法回收率在99.01%¹04.23%之间,日内、日间RSD均<11%。结论:该法操作简便、准确、重复性好,可用于临床监测帕利哌酮的血药浓度。     

帕利哌酮缓释片治疗老年精神分裂症患者的疗效和安全性研究

目的比较帕利哌酮缓释片与奋乃静片治疗老年期精神分裂症的疗效和安全性。方法将63例老年期精神分裂症患者随机分为两组,分别予帕利哌酮缓释片和奋乃静片治疗8周,治疗前后采用阳性与阴性症状量表（PANSS）评定疗效、个人和社会功能量表（PSP）评定社会功能改善情况和副反应量表（TESS）观察不良反应。结果观察组和对照组总有效率分别为84．38％和80．65％,差异无统计学意义（P〉0．05）。观察组不良反应低于对照组。结论帕利哌酮缓释片治疗老年精神分裂症疗效较好,安全性高,有利于长期巩固维持治疗。     

Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials

ABSTRACT

Objective: To assess differences in the number of days hospitalized among schizophrenic patients receiving paliperidone extended-release (paliperidone ER) during the open-label extension (OLE) phases, compared to a similar time period prior to the screening for entry into the double-blind (DB) trials conducted in the United States.

Methods: Mental health-related hospital days during the 52 weeks before entering the DB trials and during the OLE phases were compared. The mean number of hospital days per person per year in the pre- and post-periods was calculated and the statistical significance of pre-post differences was assessed using bootstrap resampling methods. Total person-years were also calculated for the pre- and post-periods to account for different lengths of observation.

Results: Patients' (n = 215) mean (?±?SD) age was 41.2 (?±?11.0) years; most were male (73.0?%?); and black (52.1 vs. 45.1?%?white). The mean (?±?SD) paliperidone ER treatment duration during the OLE phase was 167.0 (?±?145.0) days and the mean (?±?SD) daily dose was 10.5 (?±?2.0) mg. Overall, paliperidone ER patients spent an average (?±?SD) of 13.2 (?±?1.6) and 3.1 (?±?0.7) hospital days per person-year in the pre-and post-periods, respectively (mean?±?SD change 10.0?±?1.8, 95?%?CI 6.5, 13.4, p?<?0.001). Using the 2007 Federal Per Diem Base Rate (i.e., $595.09 per day), this reduction in hospital days would result in an average (?±?SD) cost savings of $5951 (?±?1071) per person per year.

Conclusions: Patients had significantly fewer hospital days in the OLE phase compared to the 1-year period prior to entering the DB trial. Paliperidone ER may play a role in reducing mental health-related hospital days and associated costs. Important study limitations include the lack of a control group, the pre-post design comparing historical data with data collected in the trials which could create a bias due to the mismatch in settings, and patients having more frequent contact with treating physicians and investigators during the trial period, which could favor the outcomes in the OLE phase. Further studies are needed to confirm these findings.     

Practical guidelines on the use of paliperidone palmitate in schizophrenia

Abstract

Objective:

Paliperidone palmitate is an atypical long-acting injectable (LAI) antipsychotic that has been approved for use in the US, EU, Australia and numerous other countries for acute and maintenance therapy of schizophrenia.

LAI antipsychotics are often viewed as a ‘last-resort’ treatment for difficult-to-treat patients, however this article considers their role more broadly in the management of partial or non-adherence in schizophrenia.     

Paliperidone for the treatment of schizoaffective disorder

Introduction: Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning.

Areas covered: Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed.

Expert opinion: Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.     

帕利哌酮缓释片联合银杏叶提取物治疗精神分裂症临床观察

目的：观察帕利哌酮缓释片联合银杏叶提取物治疗精神分裂症的临床效果。方法将77例精神分裂患者随机分为治疗组40例和对照组37例。治疗组给予察帕利哌酮缓释片联合银杏叶提取物治疗,对照组给予察帕利哌酮缓释片治疗,疗程6周。用简明精神病评定量表（ BPRS）在治疗前及治疗1、2、4、6周末评定疗效,用副反应量表（TESS）评定不良反应。结果治疗第6周末,治疗组的痊愈率为62．5％（25／40）高于对照组的35．1％（13／37）,差异有统计学意义（P＜0．05）。治疗前2组BPRS评分比较差异无统计学意义（P＞0．05）,治疗组的BPRS的评分从第1周末起明显下降（P＜0．05）,且一直持续到治疗第6周末;而对照组的BPRS评分从第2周末才开始明显下降（P＜0．01）;治疗第1、2周末,治疗组的BPRS的评分比对照组下降明显（P＜0．01）,但在第4、6周,2组BPRS的评分下降差异无统计学意义（P＞0．05）。2组不良反应发生率差异无统计学意义（P＞0．05）。2组TESS评分差异无统计学意义（ P＞0．05）。结论帕利哌酮缓释片合并银杏叶提取物治疗精神分裂症比单用帕利哌酮缓释片起效更快,但2周后BPRS减分率的差异无统计学意义,可以不必继续联合使用银杏叶提取物。     

Can semipermeable membranes coating materials influence in vivo performance for paliperidone tri-layer ascending release osmotic pump tablet: In vitro evaluation and in vivo pharmacokinetics study

One purpose of this study was to develop a paliperidone (PAL) tri-layer ascending release push–pull osmotic pump (TA-PPOP) tablet which could meet the needs of clinical applications. And another purpose was to investigate whether different coating materials influenced in vivo performance of TA-PPOP. The ascending release mechanism of this tri-layer delivery system on theory was elaborated. TA-PPOP was prepared by means of coating with cellulose acetate (CA) or ethyl cellulose (EC). Several important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviors of PAL. In vitro dissolution studies indicated that both the two formulations of different coating materials were able to deliver PAL at an ascending release rate during the whole 24 h test. The in vivo pharmacokinetics study showed that both self-made PPOP tablets with different coating had a good in vitro-in vivo correlation (IVIVC) and were bioequivalent with the brand product, which demonstrated no significant influence of the coating materials on the in vivo release acceleration of TA-PPOP.     

帕利哌酮缓释片治疗酒精所致精神障碍疗效及安全性的对照研究

目的 探讨帕利哌酮缓释片与奋乃静治疗酒精所致精神障碍的疗效和安全性.方法 共纳入55例酒精所致精神障碍患者进行8周的研究,帕利哌酮缓释片组(研究组)26例,奋乃静组(对照组)29例.在治疗前及治疗第2、4、8周末采用阳性和阴性综合征量表(PANSS)、治疗中需处理的不良反应症状量表(TESS)评定临床疗效和副反应.结果 (1)两组治疗后PANSS量表分均比治疗前降低(P＜0.01);两组间比较,研究组治疗的第4、8周末阴性症状量表分比对照组降低明显(P＜0.05);(2)研究组显效率76.9％,有效率为92.3％;对照组显效率75.8％,有效率为93.1％,疗效无差异(x2=0.63,P=0.90);(3)两组TESS评定比较,研究组的神经系统和实验室检查合计副反应的发生率较对照组低(x2=4.29,P=0.00 39x2=6.74,P=0.000 9);合用药物方面,研究组合用苯海索8例,对照组合用苯海索18例,差异有统计学意义(x2=5.39,P=0.02);研究结束时使用护肝药物,研究组3例,对照组10例,差异具有统计学意义(x2=3.99,P=0.04).结论 帕利哌酮缓释片治疗酒精所致精神障碍疗效好,副反应较奋乃静轻微.     

Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic,behavioral, biochemical,and histological aspects

Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70–98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects.     

帕利哌酮缓释片治疗精神分裂症的疗效与安全性分析

目的探讨帕利哌酮缓释片治疗精神分裂症的疗效和安全性。方法对100名精神分裂症患者进行为期8周的帕利哌酮缓释片系统治疗,在治疗期间定期进行PANSS、TESS、CGI评定以及血常规、生化系列、心电图检查。结果帕利哌酮缓释片治疗前后PANSS、CGI评分差异有统计学意义(P<0.05)。最常见的不良反应是失眠、头痛和静坐不能。结论帕利哌酮缓释片能有效治疗精神分裂症,无严重不良反应,安全性高,服药方便。