氟伏沙明抑制奥氮平体内代谢的药代动力学研究

目的　探讨细胞色素P450 1A2酶 (CYP1A2 )抑制剂氟伏沙明对奥氮平在体内代谢的影响。方法　 1 2名男性健康志愿者 ,采用自身前后对照设计 ,两次服药间隔 4周 ,口服单剂奥氮平 1 0mg;对照部分采用单剂量奥氮平 ,试验部分是在氟伏沙明连续 9天服用过程中的第 4天合用单剂量奥氮平。高效液相色谱电化学法测定奥氮平血浆浓度。结果　合用氟伏沙明后 ,奥氮平各时点的平均浓度增高 ;奥氮平的峰浓度由 1 9 5μg/L增至 2 9 1 μg/L(1 52倍 ,P <0 0 0 1 ) ,消除半衰期由 32 2h延长为46 1h(1 48倍 ,P <0 0 1 ) ,0～ 1 2 0h药时曲线下面积由 647 5μg·h 1 ·L 1 增至 1 0 55 0 μg·h 1 ·L 1 (1 65倍 ,P <0 0 0 1 ) ;而达峰时间由 3 8h缩短为 2 6h(0 69倍 ,P <0 0 1 ) ,系统清除率由 1 6 4L/h减至 8 5L/h(0 59倍 ,P <0 0 0 1 ) ,表观分布容积由 435 5L降为 2 99 2L(0 70倍 ,P <0 0 1 )。结论　氟伏沙明能明显抑制奥氮平在体内的代谢。CYP1A2可能是催化奥氮平体内代谢的主要氧化酶之一。奥氮平与涉及CYP1A2的药物合用时应注意密切观察、趋利避害     

Olanzapine counteracts stress-induced anxiety-like behavior in rats

Atypical antipsychotics, such as olanzapine, have been reported to display anxiolytic properties as shown in several preclinical and clinical studies. Furthermore, several experimental evidences have shown that olanzapine reduces fear and anxiety in activated anxiety-like behavior test such as Geller-Seifter test, ultrasonic vocalization test and stress-induced EtOH consumption. Here, we hypothesized that the anxiolytic action of olanzapine might be due to via an indirect activation of the γ-amino butyric acid (GABA)-ergic system through 3α-hydroxy-5α-pregnan-20-one [allopregnanolone (ALLO)], a potent neuroactive steroid that positively modulates the benzodiazepine-γ-aminobutyric acid type A (GABA_A)/benzodiazepine receptors complex. To address this question, we used a preclinical animal test to screen for novel anxiolytic compounds – the elevated plus-maze (EPM) – in basal condition and after 45 min restrain stress after acute or repeated (21 days) administration of olanzapine (0.5 mg/kg, i.p.). In this condition, we therefore study the effect of the 5-alpha-reductase inhibitor finasteride (FIN) (50 mg/kg) after co-administration with olanzapine. FIN is an inhibitor of steroidogenic enzymes which acts by inhibiting type II 5-alpha reductase, the enzyme that converts into 5-alpha-reduced metabolites like the GABA_A positive neuroactive steroid ALLO. Results showed an anxiolytic effect of the acute, but not of the chronic, treatment with olanzapine only in stressed rats. This anxiolytic effect was counteracted by the co-administration with FIN. These evidences suggest that the anxiolytic effects of olanzapine might be due to possible action of olanzapine on steroid function via activation of GABA system.     

奥氮平与氯氮平联合心境稳定剂治疗躁狂症对照研究

目的　比较奥氮平与氯氮平治疗躁狂症的疗效与不良反应。方法　将符合CCMD 3双相情感性精神障碍躁狂相或躁狂发作诊断标准的 78例患者 ,随机分为研究组 (奥氮平联合心境稳定剂组 ) 38例和对照组 (氯氮平联合心境稳定剂组 ) 4 0例 ,分别进行 6w的治疗和观察 ,并于入组时和治疗第 1、2、4、6w末应用BRMS各评定 1次 ,以TESS评定不良反应 ,以Beck -Rafaelsen减分率评定临床疗效。结果　研究组与对照组治疗 6w末躁狂症状均有显著性改善 ,有效率分别为 94 .7%和 92 .5 % ,两组间比较无显著性差异 (P >0 .0 5 ) ,药物不良反应研究组显著少于对照组。结论　奥氮平是一种有效的抗躁狂药物 ,不良反应少且轻     

A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study

In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin 70 mg/m²). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin 50 mg/m²). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.     

奥氮平联合曲唑酮对甲基苯丙胺所致精神障碍患者的应用价值

目的:探讨奥氮平联合曲唑酮治疗甲基苯丙胺所致精神障碍的临床应用价值。方法:选取我院2015年1月至2016年6月期间收治的72例因吸食甲基苯丙胺致精神障碍患者为研究对象,根据入院顺序将其分为曲唑酮组(曲唑酮治疗,共36例)和联合组(奥氮平联合曲唑酮治疗,共36例),均持续治疗4周。采用阳性与阴性症状量表(PANSS)、不良反应症状量表(TESS)评估两组治疗效果,并比较两组患者生活质量(GQOLI-74)改善情况。结果:两组均成功完成治疗,无中途退出或脱落病例;两组治疗4周后,PANSS量表评分均较治疗前显著降低(t=17.380,25.906;P0.05),与曲唑酮组相比,联合组PANSS量表评分降低更为明显(t=8.943,P0.05);两组均取得一定积极疗效,联合组疗效明显优于曲唑酮组(Z=2.212,P0.05);两组治疗不良反应率相较无显著差异(χ~2=1.000,P0.05),但联合组治疗后TESS评分明显低于曲唑酮组(t=2.254,P0.05);两组治疗后GQOLI-74量表评分较治疗前均有明显提高(t=2.406,5.700;P0.05),和曲唑酮组相比,联合组GQOLI-74量表评分提高更为显著(t=3.117,P0.05)。结论:奥氮平联合曲唑酮治疗甲基苯丙胺致精神障碍临床疗效较好,有助于改善患者精神障碍症状和提高生活质量,且联合治疗并不增加药副反应,值得临床推广应用和深入研究。     

奥氮平联合昂丹司琼预防非小细胞肺癌化疗所致恶心呕吐的疗效观察

目的比较奥氮平联合昂丹司琼与单用昂丹司琼预防非小细胞肺癌（NSCLC）化疗所致恶心呕吐（CINV）的效果。方法84例NSCLC患者随机分为研究组（42例）及对照组（42例）,研究组和对照组均在化疗前30min给予静脉滴注昂丹司琼8mg,研究组自化疗第1天早晨开始I：1服奥氮平10mg,连用8d,评价化疗第1周期的止吐效果。结果研究组和对照组急性呕吐的发生率分别为33．33％（14／42）和54．76％（23／42）,差异有统计学意义,P〈0．05;迟发性呕吐的发生率分别为16．67％（7／42）和47．62％（20／42）,差异有统计学意义,P〈0．01。结论奥氮平联合昂丹司琼与单用昂丹司琼相比,奥氮平联合昂丹司琼对于预防NSCLC化疗所致恶心呕吐有更好的效果,尤其是对迟发型恶心呕吐效果更为显著。     

奥氮平联合西酞普兰治疗创伤后应激障碍疗效观察

目的观察奥氮平联合西酞普兰治疗创伤后应激障碍(post-traumatic stress disorder,PTSD)的疗效及安全性。方法选择2009年1月—2011年12月58例PTSD患者随机分为奥氮平组、西酞普兰组、联合治疗组,均辅以支持性心理治疗,奥氮平组单用奥氮平治疗,西酞普兰组单用西酞普兰治疗,联合治疗组给予奥氮平与西酞普兰联合治疗。比较3组治疗前后抑郁自评量表(self-rating depression scale,SDS)和焦虑自评量表(self-rating anxiety scale,SAS)评分、平均用药量和不良反应。结果 3组患者治疗后SDS和SAS评分均显著低于治疗前(均P<0.05),治疗1周联合治疗组SDS和SAS评分显著低于奥氮平组和西酞普兰组(均P<0.05),治疗6周3组SDS和SAS评分差异均无统计学意义(均P>0.05)。联合用药组奥氮平平均用药量(7.6±2.3)mg/d,显著低于奥氮平组(15.8±4.2)mg/d,差异有统计学意义(P<0.05);联合用药组西酞普兰平均用药量(21.7±3.1)mg/d,显著低于西酞普兰组(30.6±4.5)mg/d,差异有统计学意义(P<0.05)。3组不良反应主要为嗜睡、食欲增加、体重增加,均较轻微,患者均能耐受,不需特殊处理。结论奥氮平联合西酞普兰治疗PTSD比单一用药起效早且用药量小,安全性良好。     

奥氮平对精神分裂症患者甲状腺素和泌乳素的影响

目的 探讨奥氮平对精神分裂症患者甲状腺素和泌乳素水平的影响.方法 对服用奥氮平治疗的32例精神分裂症患者,于治疗前后检测甲状腺各项生化指标及泌乳素水平,并进行对比分析.结果 治疗后入组被试游离三碘甲状腺原氨酸、游离甲状腺素水平较治疗前显著降低（P＜0.05）,泌乳素水平较治疗前显著升高（P＜0.01）.结论 奥氮平可致精神分裂症患者的甲状腺激素水平下降,泌乳素升高,建议临床应对服用奥氮平患者定期检测甲状腺功能和泌乳素水平.     

奥氮平和阿立哌唑对首发精神分裂症患者血脂影响的对比研究

目的:探讨奥氮平和阿立哌唑对首发精神分裂症患者脂代谢影响的差异,评价药物的安全性。方法:将127例首发精神分裂症住院患者随机分为奥氮平组(63例)和阿立哌唑组(64例),于治疗前及治疗后第8周末测定患者血总胆固醇(TC)、甘油三酯(TG)水平。结果:经治疗8周后,奥氮平组患者TC、TG升高明显,P<0.05或P<0.01;阿立哌唑组患者TC、TG升高不明显,P>0.05。结论:阿立哌唑对患者的血脂影响较小,奥氮平治疗首发精神分裂症患者可引起血脂明显异常,在治疗过程中应采取必要的干预措施。     

奥氮平与阿立派唑对首发精神分裂症糖代谢影响的对照研究

目的:了解奥氮平与阿立派唑对首发精神分裂症糖代谢的影响。方法:共调查首次发病的住院精神分裂症患者172例,随机给予奥氮平或阿立派唑治疗。分别在两类药物治疗前、治疗后第12周末进行空腹血糖以及口服葡萄糖耐量试验测定。结果:在172例住院首发精神分裂症患者中,奥氮平组86例,糖代谢异常发生率33.7%,糖尿病发生率16.3%;阿立派唑组86例,糖代谢异常发生率3.5%,糖尿病发生率0%。奥氮平与阿立派唑相比引起精神分裂症患者糖代谢异常有显著性差异(P=0.000)。结论:奥氮平比阿立派唑引起精神分裂症患者糖代谢异常的发生率高,应定期监测血糖。