Physicochemical analysis and nonisothermal kinetic study of sertraline–lactose binary mixtures

In the present study the physicochemical stability of sertraline with lactose was evaluated in drug-excipient binary mixtures. Different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy, and mass spectrometry were applied to confirm the incompatibility. The final aim of this study was to evaluate the kinetic parameters using a fast and sensitive DSC method. Solid-state kinetic parameters were derived from nonisothermally stressed physical mixtures using different thermal models such as Friedman, Flynn–Wall–Ozawa, and Kissinger–Akahira–Sunose. Overall, the instability of sertraline with lactose was successfully evaluated. Further confirmation was made by tracking the Maillard reaction product of sertraline and lactose by mass spectrometry. DSC scans provided important information about the stability of sertraline in solid-state condition and also revealed the related thermokinetic parameters in order to understand the nature of the chemical instability.     

艾司西酞普兰治疗老年抑郁症的疗效

目的：探讨艾司西酞普兰治疗老年期抑郁症的疗效与安全性。方法：61例老年期抑郁症患者随机分为艾司西酞普兰组31例和舍曲林组30例治疗6周,采用汉密尔顿抑郁量表（HAMD）,临床大体印象量表（CGI）,治疗中出现的症状量表（TESS）评定疗效及不良反应。结果：治疗6周,两组各量表评分均较治疗前有显著改善（P〈0.01）,艾司西酞普兰组治疗1周比舍曲林组改善显著（P〈0.05）,提示西酞普兰组起效快,有效率93.5%,舍曲林组为90%,两组疗效相当（P〉0.05）,两组不良反应轻微,无需特殊处理。结论：艾司西酞普兰治疗老年期抑郁症疗效显著,安全性高,起效快,耐受性好。     

舍曲林治疗强迫症对照研究的Meta分析

目的探讨舍曲林与对照药治疗强迫症的疗效差异。方法：应用Meta分析对11项舍曲林治疗强迫症对照研究的文献进行再分析,评价其合并效应量大小和综合显著性检验。结果：舍曲林治疗前后的自身对照,合并效应量d=2.36,95%CI（2.06,2.66）,综合显著性检验（χ2=15.53,P〈0.01）,提示舍曲林治疗强迫症前后,症状学变化有非常显著性差异,效应极强;舍曲林与对照药在治疗第2周末和治疗结束后的组间比较,分别为d=0.02,95%CI（﹣0.14,0.18）,（χ2=0.21,P〉0.05）;y合并=﹣0.07,95%CI（﹣0.64,0.50）,（χ2=0.24,P〉0.05）。提示舍曲林与对照药疗效相仿。结论：舍曲林改善强迫症状疗效显著,与对照药治疗强迫症的疗效相仿。     

国产舍曲林片的人体药动学及生物等效性研究

 目的评价国产和进口舍曲林片在中国人群中的生物等效性。方法采用液相色谱-质谱联用法测定18名健康受试者po100 mg舍曲林片后血浆中的舍曲林浓度。采用统计软件计算药动学参数,并评价其生物等效性。结果国产舍曲林片和进口片的药动学参数AUC_0-100分别为(836.73±427.15)和(839.55±423.66)μg·h·L^-1,实测ρ_max为(27.71±9.67)和(26.34±8.21)μg·L^-1,实测t_max为(5.78±1.11)和(5.83±1.20)h,MRT为(31.73±3.59)和(32.83±3.89)h,t_1/2为(28.89±6.32)和(31.13±9.63)h。国产舍曲林片和进口片的相对生物利用度为(99.52±8.87)%。结论经统计学分析,国产舍曲林片和进口片具有生物等效性。     

舍曲林对高血压伴焦虑抑郁患者血压昼夜节律及心率变异性的影响

目的探讨舍曲林对伴焦虑抑郁原发性高血压（essential hypertension,EH）患者血压昼夜节律及心率变异性（heart tate variability,HRV）的影响。方法选择2009年6月至2010年5月我院收治的EH伴焦虑抑郁患者61例,随机分为实验组（卡托普利＋舍曲林）和对照组（卡托普利＋安慰剂）,并随访8周,观察2组治疗前后焦虑自评量表（SAS）和抑郁自评量表（SDS）评分,坐位血压,动态血压,血压昼夜节律及动态心电图的情况。结果①实验组治疗后SAS、SDS评分明显降低（P〈0.01）,而对照组无明显变化,两组治疗后相比差异有统计学意义;②治疗后实验组动态血压各项指标均较对照组降低更加明显（P〈0.05）。实验组非勺型血压昼夜节律发生率明显降低,而对照组无明显变化,对照组与实验组治疗后相比差异有统计学意义（64.5%vs 36.7%,χ^2=4.731,P〈0.05）。③治疗后实验组HRV时域指标（SDNN、SDANN、RMSSN、PNN50）明显高于对照组（P〈0.01）。结论抗焦虑抑郁剂舍曲林能有效缓解伴焦虑抑郁EH患者的焦虑抑郁情绪,可提高降压疗效,改善血压昼夜节律及HRV。     

Effect of sertraline on ouabain‐induced arrhythmia in isolated guinea‐pig atria

Background: The effect of sertraline a selective serotonin reuptake inhibitor antidepressant was studied on ouabain‐induced toxicity (arrhythmia) in spontaneously beating isolated guinea‐pig atria. Methods: The guinea‐pig atrium was dissected out and suspended in modified Krebs solution under physiological conditions. Drugs were added into solutions. The changes in rate and force of contractions were measured using a physiograph. Results: Sertraline (2–16 µg/mL) caused a dose‐dependent decrease in the rate of contractions (17–46%) and in the contractile force (26–48%). Ouabain alone (1.2 µg/mL) produced arrhythmia at 7.8 min and asystole at 22 min. Pre‐ administration of the atria with sertraline (8 µg/mL) significantly increased the time required to produce arrhythmia by ouabain to 20.5 min, prolonged the beating of atria to more than 64.5 min and delayed the occurrence of asystolia. The pattern of contractile force induced by sertraline + ouabain was more regular than that produced by ouabain alone. Conclusions: These findings indicate that sertraline produces direct cardiac action, probably due to the inhibition of cardiac Na⁺ and Ca²⁺ channels. Our results suggest that sertraline may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain‐induced arrhythmia. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.