文拉法辛缓释剂治疗伴或不伴高血压的老年期抑郁症对照研究

目的:探讨文拉法辛缓释剂对伴有高血压的老年期抑郁症的疗效和安全性。方法:使用文拉法辛缓释剂对30例伴有高血压的老年期抑郁症和30例无高血压的老年期抑郁症患者进行为期6周的对照治疗,在治疗前及治疗后第1、2、4、6周末评定汉密尔顿抑郁量表(HAMD 17项),并进行临床疗效评定, 监测血压,记录不良反应。结果:高血压组和非高血压组患者的HAMD评分均从第1周末起明显下降(P< 0．05或P<0．01),且一直持续至治疗第6周末。两组6周末的有效率和临床治愈率差异无显著性(P> 0．05)。高血压组患者使用文拉法辛缓释剂治疗后第2周末收缩压变化值显著高于非高血压患者(0．9±0．4, 0．6±0．5,P=0．01)。两组间的不良反应发生率差异无统计学意义(P>0．05)。结论:文拉法辛缓释剂治疗老年期抑郁症疗效肯定,不良反应少,对血压无明显影响。     

博乐欣与阿米替林治疗抑郁障碍对照观察

目的：探讨博乐欣与阿米替林对抑郁障碍的疗效及副反应。方法：对５０例抑郁障碍患者应用博乐欣（２５例）与阿米替林（２５例）进行对照治疗,疗程６周。     

功能性消化不良患者的心理测评及抗抑郁治疗

目的：探讨心理异常与功能性消化不良(FD)发病的关系，并探讨抗抑郁治疗对FD患者的疗效。方法：采用焦虑自评量表(SAS)和抑郁自评量表(SDS)对100例FD患者及100名健康对照组进行心理测评，比较2组焦虑、抑郁的发生率；采用评分法对FD患者进行症状评分，随机将心理测评异常的FD患者分为常规组及综合组，分别给予抗消化不良药物及在此基础上加用抗抑郁药文拉法辛治疗，比较2种治疗方法的总有效率；将综合治疗有效的病例随机分成维持组及停药组，维持组继续给予文拉法辛维持量治疗，观察6mo中2组的复发率。结果：FD组患者焦虑及抑郁状态发生率明显高于健康组；综合组有效率高于常规组；文拉法辛6mo维持治疗复发率低于疗程结束后即停药者。结论：焦虑、抑郁的心理异常是FD发病的危险因素，但用抗抑郁治疗可提高FD患者常规治疗的有效率，6mo维持治疗能有效降低FD复发率。     

药品行政保护品种介绍:神经和精神系统药物(一)(待续)

文拉法辛缓释胶囊　通用名 :文拉法辛 (venla faxine)缓释胶囊。商品名 :怡诺思 (Efexor)缓释胶囊。化学名 :(R/S) 1 [2 (二甲胺 ) 1 (4 甲氧苯基 )乙基 ]环己醇盐酸盐。结构式见图 1。图 1　文拉法辛结构式　　　Fig 1　Structureofvenlafaxine　　申请日 :1999年 4月 16日。申请人 :荷兰AHP制药有限公司。申请号 :A NL 990 4 16 10。授权号 :B NL 9912 2 32 1。授权日 :1999年 12月 2 3日。法定行政保护期 :从授权之日起 7.5a ,到 2 0 0 7年 6月2 3日止。专利介绍 :欧洲专利第 0 12 2 6 6 9号。商标注册 :在我国注册的商标为怡诺…     

人血浆中文拉法辛浓度的HPLC测定及其药物动力学

建立了HPLC-荧光法测定文拉法辛的血药浓度.采用液液萃取处理血浆样品,色谱柱为C8柱,流动相为乙腈-磷酸盐缓冲液(30:70,pH 5.5),激发和发射波长分别为276和598nm,流速1.5ml/min.文拉法辛在5～2000ng/ml的浓度范围内线性关系良好.方法提取回收率为96.9%～104.3%,日内和日间RSD均小于8%.10名健康志愿者空腹单剂量口服150mg盐酸文拉法辛缓释胶囊,药物动力学参数Cmax、Tmax、AUC0→∞、t1/2分别为(168±12.3)ng/ml、(6.1±1.8)h、(4510±1462)ng·h·ml-1和(5.7±0.7)h.     

HPLC-MS同时测定4种新型抗抑郁药物的血药浓度

目的:建立一种快速灵敏的同时测定血浆中氟西汀、西酞普兰,帕罗西汀及文拉法辛浓度的 HPLC-MS 方法,监测这4种药物的血药浓度,为临床用药提供依据。方法:以氟伏沙明作为内标,样品碱化后固相萃取,用 MACHEREY-NAGEL C_(18)反相色谱柱(4.6 mm×250 mm,5μm,Germany)进行分离,以乙腈-缓冲盐(30 mmol 醋酸铵和0.6‰甲酸)(65:35)为流动相,柱温40℃,流速0.85 mL·min~(-1)。采用质谱电喷雾电离源(ESI)将样品离子化,选择性离子监测(SIM)准分子离子峰。结果:氟西汀、西酞普兰、帕罗西汀,文拉法辛及内标氟伏沙明在9 min 内完全分离;各物质在5～1000 ng·mL~(-1)时线性关系良好,相关系数均大于0.9964;萃取回收率均大于73.2%;方法回收率均大于95.0%;最低检测浓度:氟西汀0.5 ng·mL~(-1)、西酞普兰0.3 ng·mL~(-1)、帕罗西汀0.3 ng·mL~(-1),文拉法辛0.1 ng·mL~(-1);日内日间变异系数均小于15%。结论:本方法简便快速,灵敏准确,可用于血药浓度的临床监护、中毒分析,药物动力学以及代谢机制的研究。     

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

高效液相色谱-串联质谱法测定人血清中文拉法辛和O-去甲基文拉法辛浓度的不确定度评价

目的：评价高效液相串联质谱（Liquid chromatography tandem mass spectrometry,LC-MS/MS）法测定人血清中文拉法辛和O-去甲基文拉法辛浓度的不确定度。方法：对可能会引入不确定度的步骤进行分析,包括测量重复性、样品称量、溶液配制、样品处理、仪器允差、基质效应、提取回收、标准曲线拟合等,评估扩展不确定度。结果：文拉法辛低（12 ng·mL^-1）、中（120 ng·mL^-1）、高（300 ng·mL^-1）浓度质控样品的拓展不确定度分别为：U_L=0.847 ng·mL^-1,U_M=7.518 ng·mL^-1,U_H=20.776 ng·mL^-1;O-去甲基文拉法辛低（60 ng·mL^-1）、中（600 ng·mL^-1）、高（1 500 ng·mL^-1）浓度质控样品的拓展不确定度分别为：U_L=11.666 ng·mL^-1,U_M=91.479 ng·mL^-1,U_H=254.523 ng·mL^-1（P=95%,k=2）。结论：LC-MS/MS法测定人血清中文拉法辛和O-去甲基文拉法辛浓度的不确定度主要来源于标准曲线拟合、基质效应和提取回收过程。选择合适的同位素氘代内标浓度能够有效降低标准曲线拟合过程引入的不确定度。     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.