盐酸昂丹司琼片在健康人体的生物等效性研究

目的:研究两种盐酸昂丹司琼片在中国健康人体的生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服(8 mg)盐酸昂丹司琼试验制剂与参比制剂,采用液-质联用法测定血浆中昂丹司琼的血药浓度,应用SPSS 13.0统计软件进行统计分析。结果:试验制剂与参比制剂中昂丹司琼的主要药动学参数,Cmax分别为(33±8)和(32±8)μg/L,tmax分别为(1.5±0.3)和(1.5±0.4)h,AUC0~24分别为(176±67)和(168±58)μg.h.L-1,AUC0~∞分别为(188±70)和(182±63)μg.h.L-1。试验制剂对参比制剂的相对生物利用度为(103.2±10.0)%。结论:两种盐酸昂丹司琼片剂具有生物等效性。     

不同剂量地塞米松对腹腔镜胆囊切除术患者术后恶心呕吐预防效果的临床观察

目的探讨地塞米松预防腹腔镜胆囊切除术(LC)术后恶心呕吐(PONV)的效果,并寻找应用地塞米松的最小有效剂量。方法选择150例患者,随机分为5组(n=30)。分别于麻醉诱导前即刻静脉注射地塞米松0.05mg/kg(D0.05组)、地塞米松0.1mg/kg(D0.1组)、地塞米松0.2mg/kg(D0.2组)、恩丹西酮4mg(O组)和同容积生理盐水(S组)。观察记录手术后0～24h内患者PONV情况、抗恶心呕吐药物使用情况。结果 D0.1组、D0.2组与S组比较:术后0～24h内总的PONV的发生率明显降低,差异具有统计学意义(P<0.01),总需要抗恶心呕吐药物治疗的患者比例亦降低,差异具有统计学意义(P<0.05)。D0.1组与D0.2组比较差异没有统计学意义(P>0.05)。D0.05组S组比较差异没有统计学意义(P>0.05)。D0.1组与D0.05组比较,术后0～24h时内总的PONV的发生率明显降低,差异具有有统计学意义(P<0.01),需要抗恶心呕吐药物治疗的患者比例亦降低,差异具有统计学意义(P<0.05)。D0.1组与O组比较:术后0～24h内PONV发生率降低(P<0.05)。结论静脉注射地塞米松0.1mg/kg能有效地预防LC后PONV发生。     

不同厂家盐酸昂丹司琼片的溶出度考察

目的对3个不同厂家所生产的盐酸昂丹司琼片体外溶出度进行了考察,为临床用药提供参考。方法根据《中华人民共和国药典》(2010版)中盐酸昂丹司琼片的溶出度实验项下要求,采用浆法测定溶出度,紫外-可见分光光度法测定吸光度,对照品法计算溶液中盐酸昂丹司琼浓度。利用Excel软件计算累积溶出百分率及溶出参数,并进行比较分析。结果 3个厂家盐酸昂丹司琼片的体外溶出度均符合药典规定,但各自间存在一定差异。结论不同厂家盐酸昂丹司琼片的溶出情况存在一定差异。     

Ondansetron and seizures

Experimental studies suggest that 5‐hydroxytryptamine (5‐HT) receptors play a role in epileptogenesis and seizure propagation. Ondansetron, a 5‐HT₃ receptor antagonist, has been reported to have proconvulsant and anticonvulsant effects in animals. We describe three patients who developed seizures after receiving ondansetron. There were two females and one male. Ages ranged from 38–56 years. None had a previous or family history of seizures. Four milligrams (mg) of ondansetron was given intravenously for severe nausea and vomiting in association with migraine, gastritis, and diabetic ketoacidosis. A generalized tonic–clonic seizure occurred in each patient—12, 15, and 22 min after injection. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) were normal in all patients. Although no antiepileptic drugs were given, none had seizure recurrence subsequently. The temporal relationship between ondansetron administration and seizures, lack of EEG or MRI abnormalities, and absence of seizure recurrence suggest that the seizures were causally related to ondansetron in our patients.     

昂丹司琼与格拉司琼预防心脏手术后恶心呕吐的随机对照研究

目的 探讨预防心脏手术后恶心呕吐(PONV)的方法,对比研究昂丹司琼和格拉司琼对心脏PONV的影响.方法 选择气管内插管全身麻醉下行心脏手术的患者90例,随机分成三组,每组各30例.以双盲方式按下述方法给药:Ⅰ组麻醉诱导前静脉注射昂丹司琼4 mg(溶于0.9%NaCl溶液加ml);Ⅱ组麻醉诱导前静脉注射格拉司琼3 mg(溶于0.9%NaCl溶液20 ml);Ⅲ组麻醉诱导前静脉注射0.9%NaCl溶液20 ml.术后12、24 h观察记录患者的PONV程度并进行比较.结果 Ⅰ组术后12 h PONV发生率为20.0%(6/30),术后24 h发生率为26.7%(8/30);Ⅱ组术后12 hPONV发生率为20.0%(6/30),术后24 h发生率为23.3%(7/30);Ⅲ组术后12 h PONV发生率为72.4%(21/29),术后24 h发生率为79.3%(23/29).Ⅰ、Ⅱ组术后12、24 hPONV发生率显著低于Ⅲ组(P＜0.01),Ⅰ组和Ⅱ组比较差异无统计学意义(P＞0.05).结论 昂丹司琼和格拉司琼对预防心脏PONV均有较好效果,均能有效地降低心脏PONV的发生率,利于患者恢复.     

昂丹司琼对蛛网膜下腔使用吗啡导致的皮肤瘙痒的预防作用

目的:本随机、双盲、对照、前瞻研究的目的旨在了解昂丹司琼对蛛网膜下腔使用吗啡导致的皮肤瘙痒是否具有预防作用。方法选择70例拟在腰麻下行开腹全宫切除术或子宫肌瘤剔除术的ASAI-II级成年患者,分为2组:昂丹司琼组(O组)患者于腰麻前30分钟给予静脉注射昂丹司琼4mg;对照组(C组)患者在相同时间点静脉注射等体积生理盐水。于患者到达恢复室、术后2、4、8及24小时评价患者的皮肤瘙痒程度、静息VAS评分,并在两组之间进行比较,p<0.05为差异有统计学意义。结果:O组患者术后皮肤瘙痒总发生率及术后8h之内的各记录时间点的皮肤瘙痒程度显著低于C组患者(P<0.01)。严重的,需要药物治疗的皮肤瘙痒只发生于C组患者(11%)。两组患者术后各观察时间点的VAS评分之和无显著差异。结论:给予蛛网膜下腔应用吗啡的患者预先使用昂丹司琼可有效的降低术后皮肤瘙痒的发生率和严重程度,同时并未影响蛛网膜下腔应用吗啡的镇痛效果。     

Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile, and cost

Background: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. Methods: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. Results: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9-9 percent). Tropisetron is the least expensive one ($95.3 per cycle) according to current prices in Turkey. Conclusions: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.     

Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: Implications for a possible antipsychotic action of ondansetron

Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT₃ receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.     

Temperature,food intake,and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats

This study investigated three physiologic functions known to be modulated by serotonin — temperature, food intake and locomotor activity — using the 5-HT₃ receptor agonist,m-chlorophenylbiguanide (m-CPBG), and two 5-HT₃ antagonists, MDL-72222 and ondansetron. m-CPBG produced dose-dependent elevations in rectal temperature. MDL-72222, which had no effects on temperature when given alone, significantly attenuated m-CPBG-induced hyperthermia. Food intake in food-deprived rats was reduced during the first hour by the highest dose of m-CPBG. Food intake was also dose-dependently reduced by MDL-72222; m-CPBG plus MDL-72222 led to greater reductions in food intake. Food intake in freely fed rats was unaffected by m-CPBG or MDL-72222. Locomotor activity was unaffected by m-CPBG, but was dose-dependently reduced by MDL-72222, an effect which may have contributed to its hypophagic effects. Ondansetron, used in ten-fold lower doses than MDL-72222, was inactive in all of these paradigms. These data: (1) provide some evidence for 5-HT₃ receptor-mediated changes in temperature; (2) are in agreement with two prior studies which reported locomotor activity reductions following 5-HT₃ antagonists; but (3) do not support an important role for 5-HT₃ receptors in the regulation of food intake in rats.     

格拉司琼和恩丹西酮预防顺铂所致消化道反应的随机对照研究

目的 观察并比较格拉司琼与恩丹西酮在预防顺铂所致的消化道反应的疗效和毒性反应。方法 采用随机自身前后对照试验设计，将37例接受顺铂联合化疗的肺癌患者，分为AB和BA两组，AB组第1周期用A方案（盐酸格位司琼3mg静注）每日1次，连用5d，第2周期用B方案（盐酸恩丹西酮8mg静注）每12h 1次，连用5d;BA组第1周期用B方案，第2周期用A方案，前后两周期化疗方案完全相同。结果 A，B方案均有良好的止吐疗效，在呕吐控制率，平均呕吐次数，恶心控制率及食欲影响方面两方案无统计学差异（P＞0．05）。两方案毒副反应均较小，可以耐受。结论 格拉司琼与恩丹西酮预防顺铂所致的消化道反应均有较好的疗效，毒副反应低。格拉司琼价格较低廉，更适合临床应用。