盐酸舍曲林片与原研制剂溶出一致性及药典方法合理性的研究

目的 考察8厂家盐酸舍曲林片与原研制剂溶出行为的一致性,探讨中国药典方法的可行性。方法 分别以0.1 mol·L^-1盐酸（pH=1.2）、乙酸盐缓冲液（pH=4.5）、磷酸盐缓冲液（pH=6.8）和水为溶出介质,选用中国药典溶出度色谱条件考察溶出曲线,采用相似因子法评价8厂家产品在各介质中与原研制剂溶出行为的相似性。结果 8厂家的仿制药与原研制剂在不同介质中溶出曲线差异较大,说明各企业的处方工艺差异较大;在pH=4.5介质、75 r·min^-1条件下原研和各厂制剂溶出量在15 min内均>85%。结论 通过不同介质溶出曲线的比较和f₂的计算,仿制药与原研制剂存在较大差异,建议企业改进工艺。同时中国药典的溶出条件有待商榷,建议国家药典委员会参考国外药典标准,修改转速或限度。     

舍曲林早期预防卒中后抑郁对急性脑梗死患者功能康复的影响

目的:观察在脑梗死患者急性期预防性给予抗抑郁药盐酸舍曲林片对卒中后抑郁(PSD)的发生率和神经功能康复、日常生活能力以及认知功能的影响。方法:将65 例首发脑梗死患者随机分为对照组(n=32)和干预组(n=33)。干预组于入院72 h后每晚予以盐酸舍曲林片口服,对照组不给予抗抑郁药处理,治疗疗程为12周。在治疗前、治疗4周末、治疗12周末采用美国国立卫生院神经功能缺损评分量表(NIHSS)、改良Barthel指数量表(MBI)、汉密尔顿抑郁量表(HAMD)、蒙特利尔认知评估量表(MoCA)分别观察患者的神经功能缺损状态、日常生活能力、PSD发生率以及认知功能水平。结果:在治疗4周和12周末,干预组的NIHSS评分分别为(12.67±1.71)和(6.24±1.31),显著低于对照组;而干预组的MBI评分分别为(80.48±6.17)和(92.21±3.91)显著高于对照组的(76.09±4.89)和(85.37±6.71)。干预组在4周末和12周末的PSD发生率分别为18.2.%和12.1%,显著低于对照组的43.8%和37.5%。干预组的MoCA评分分别为(23.82±6.14)和(26.75±5.61),显著高于对照组的(21.75±4.92)和(23.65±3.89)。结论:在脑梗死急性期预防性给予舍曲林治疗,能显著降低卒中后抑郁的发生率,促进患者的神经功能康复,提高其日常生活能力以及认知功能水平。     

安非他酮与舍曲林治疗抑郁症疗效比较

目的比较安非他酮与舍曲林对抑郁症的疗效及其安全性。方法125例抑郁症分为2组。安非他酮组63例[男性30例,女性33例,年龄(36±s 13)岁,本次抑郁病期(3±5)mo]予安非他酮300～450 mg·d~(-1),po,bid;舍曲林组62例[男性28例,女性34例,年龄(40±11)岁,本次抑郁病期(3±4)mo]予舍曲林50～100 mg,po,qd;均6 wk为一个疗程。结果对抑郁症状的治疗,安非他酮组显效率71%,舍曲林组显效率74%,2组疗效比较差异无显著意义(P>0.05);对伴随焦虑症状的治疗,安非他酮组显效率48%,舍曲林组显效率45%,2组疗效比较差异无显著意义(P>0.05)。整体药物不良反应发生率2组相当。结论安非他酮与舍曲林疗效相当,能有效治疗抑郁症及伴随焦虑症状,不良反应轻微。     

舍曲林联合普瑞巴林治疗老年带状疱疹后神经痛镇痛疗效的研究

目的评价舍曲林联合普瑞巴林治疗老年带状疱疹后神经痛的临床疗效。方法 60例老年带状疱疹后神经痛患者随机分为对照组(n=32)和试验组(n=28)。对照组用普瑞巴林150 mg·d-1,试验组在对照组基础上加用舍曲林50mg·d-1,2组均常规营养神经药物治疗及物理治疗。治疗前、治疗后4周用视觉模拟评分(VAS)评估患者的疼痛强度变化,中文版简明健康测量量表(SF-36)评定生活质量的变化。结果 2组治疗后疼痛强度均较治疗前显著降低(P<0.05),试验组疼痛缓解显著高于对照组(P<0.05)。试验组在6个领域的生活质量较对照组明显改善(P<0.05)。2组不良反应发生率差异无统计学意义。结论舍曲林联合普瑞巴林能提高老年带状疱疹后神经痛的疗效。     

使用5-羟色胺再摄取抑制剂150例病人的不良反应分析

目的 :了解选择性 5 羟色胺再摄取抑制剂(SSRIs)氟西汀、舍曲林、帕罗西汀的不良反应特点 ,增强对 5 羟色胺 (5 HT)综合征的认识。方法 :用自制不良反应调查表对 15 0例使用上述 3药的病人发生的药物不良反应进行调查。结果 :发现有 7例出现 5 HT综合征 ,共同表现意识模糊、肌张力增高、反应迟钝、主动性减退、震颤、遗忘 ,停药才消失 ,其中 1例曾误诊为老年性痴呆 ;另 143例中失眠、头痛(头晕 )、烦躁等不良反应 ,氟西汀组高于其他 2组 ,余无差异 ,此类不良反应能自行减轻或消失。结论 :应提高对SSRIs药物不良反应的认识 ,对 5 HT综合征要与原有抑郁症状加重仔细鉴别     

Biochemical profile in patients with anxious depression under the treatment with serotonergic antidepressants with different mechanisms of action

The pharmacodynamics of serotonergic antidepressants that differentially influence serotonin reuptake transporters is poorly investigated. The aim of this study was to compare the biochemical profiles in patients with anxious depression under the treatment with tianeptine, a serotonin reuptake enhancer, and sertraline, a selective serotonin reuptake inhibitor. Platelet monoamine oxidase (MAO) and serum amine oxidase (AO) activities, concentration of middle-mass endotoxic molecules (MMEM) and parameters that characterize the functional properties of serum albumin were investigated in 43 patients with anxious depression (ICD-10: F 32.1 and F 33.1). It was established that, in comparison with healthy controls, patients with anxious depression were characterized by the significant increase in MAO activity (by 95%), MMEM concentration (by 86%), and a significant decrease in AO activity (by 43%) and also in functional albumin activity. The results of the study show that both tianeptine and sertraline are equally effective in the treatment of anxious depression. The present biochemical investigation, however, suggests that the underlying biochemical changes are more complete following tianeptine treatment.     

Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes

AIMS: The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. METHODS: The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. RESULTS: The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent Km values for the high-and low-affinity components were 1.9 and 88 microm and V max values were 33 and 554 pmol min-1 mg-1 protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. CONCLUSIONS: The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway.     

人血浆中舍曲林浓度的LC-MS测定

建立了人血浆中舍曲林浓度的LC-MS测定方法。以阿普唑仑为内标,采用ODS柱,流动相为30mmol/L乙酸铵溶液（含0.5%甲酸和0.02%三氟乙酸）-乙腈（62∶38）,流速1.6ml/min,分流比为2∶1。采用电喷雾电离源正离子模式,选择性监测质荷比（m/z）为159（舍曲林）和311（阿普唑仑）的离子峰。样品经氨水碱化后用叔丁基甲醚提取。舍曲林的线性范围为0.24～19.52ng/ml,提取回收率和方法回收率均大于80%,批间和批内的RSD均小于12%。     

舍曲林联合阿立哌唑治疗老年抑郁症对照研究

目的 探讨舍曲林联合阿立哌唑治疗老年抑郁症的临床疗效和安全性.方法 将60例老年抑郁症患者随机分为两组,每组30例,两组均口服舍曲林治疗,研究组联合阿立哌唑治疗,观察6周.于治疗前及治疗第1周、2周、4周、6周末采用汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应.结果 治疗后两组汉密顿抑郁量表评分均较治疗前显著下降(P＜0.05或0.01),同期研究组均较对照组下降更显著(P＜0.01);治疗6周末研究组显效率及总有效率均高于对照组,但差异无显著性(P＞0.05);两组不良反应较轻微,发生率差异无显著性(P＞0.05).结论 舍曲林联合阿立哌唑治疗老年抑郁症疗效显著,起效快,安全性高,依从性好,值得临床推广应用.