西沙必利对糖尿病胃肠运动功能障碍的影响

观察西沙必利对糖尿病患者胃肠运动功能障碍的影响。通过胃肠测压与胃电图同步检测的方法观察糖尿病患者服用西沙必利前后消化间期胃肠动力及胃电图的变化。结果服药前30例糖尿病患者中有21例缺乏MMC3期。服药2周后，21例中有11例恢复正常MMC3期。MMC3期和2期收缩液振幅较治疗前明显升高。胃电图治疗后表现为主频比（PDF）的增加。结论：西沙必利可促进消化间期胃肠动力，有利于糖尿病胃轻瘫的治疗。     

Meta-analysis of randomized controlled trials on the benefits and risks of using cisapride for the treatment of gastroesophageal reflux in children

BACKGROUND AND AIM: Gastroesophageal reflux is a common problem in infancy. Cisapride is a commonly used therapy for gastroesophageal reflux in children. In view of recent concern regarding adverse effects this study aims to evaluate the benefits and risks of cisapride for the treatment of gastroesophageal reflux in children. METHODS: A meta-analysis of randomized controlled trials of cisapride using a random-effects model. RESULTS: Ten trials involving 415 children were identified. There was no evidence of a significant reduction in vomiting severity with cisapride as measured by a clinical score (five trials, standardized weighted mean difference -0.18; 95% confidence interval (CI) -0.51 to 0.15). Twenty-four-hour esophageal pH monitoring data showed the mean reflux index was significantly lower in the children treated with cisapride compared with controls (five trials, weighted mean difference -6.24; 95% CI -8.81 to -3.67). With cisapride treatment, there was no reduction in the mean number of reflux episodes lasting greater than 5 min (three trials, weighted mean difference -0.72; 95% CI -1.92 to 0.47) or in the number of children with esophagitis at final follow up compared with baseline (two trials, relative risk 0.80; 95% CI 0.40 to 1.61). There was no significant difference in reported side-effects or adverse events (six trials, relative risk 1.16; 95% CI 0.95 to 1.41). CONCLUSIONS: No clinically important benefits of cisapride in children with gastroesophageal reflux have been demonstrated. Nor was there any evidence of adverse or harmful events.     

兔血浆及脏器中西沙必利薄层扫描测定法

目的建立薄层扫描法测定血浆中西沙必利浓度.方法样品经醋酸乙酯提取后,乙醇定容,点样于硅胶GF254-硅胶G(5:3)板后,以二氯甲烷-甲醇(10:0.8)为展开剂,展开,斑点于岛津CS-930扫描仪λs=307nm,λR=360nm处进行扫描.结果标准曲线在0.20～10.0μg范围内线性关系良好,平均回收率为97.92%,RSD=3.8%(n=9).用此法测定了家兔灌胃西沙必利后的血浆浓度,绘制了药-时曲线.结论本法灵敏、易行,可用于药代动力学研究及临床监测.     

胃肠促动力药治疗功能性消化不良的成本-效果分析

目的：比较莫沙必利、西沙必利、氯波必利及多潘立酮治疗功能性消化不良的疗效与药物经济学成本。方法：将272例功能性消化不良患者，随机分成4组。A组予莫沙必利5mg，3次／d；B组予西沙必利10mg，3次／d；C组予氯波必利0.68mg，3次／d；D组予多潘立酮10mg，3次／d。均口服治疗，疗程均为4周，运用药物经济学的成本一效果分析方法进行评价。结果：4种治疗方案的成本一效果比分别为1．05，2.24，1．49，0.85。结论：A组治疗方案的效果最佳。     

小肠气钡双对比造影法的研究

目的:研究一种新的、简便易行的小肠双对比造影法—无管法快速小肠气钡双对比造影法。初步评价其效果,并与传统口服钡剂小肠造影法相比较,同时比较西沙必利与胃复安在小肠双对比造影中的药效。方法:将产气粉装入小肠溶胶囊,口服并在小肠内崩解,释放二氧化碳气体,配合口服钡剂及西沙必利,形成小肠双对比像。选取100例拟行小肠造影检查者,随即分为研究组和对照组,研究组67例采用本法,对照组33例采用口服钡剂法加肌注胃复安。结果:研究组53例效果满意,12例基本满意,2例未观察到明显双对比效果,其中1例因吞咽困难无法检查,总有效率97.02%,平均检查时间34.63±16.66m in;对照组均为单钡造影效果,平均检查耗时77.12±32.98m in;两种检查方法耗用时间及两种药物的效果在统计学上具有显著性差异(P<0.01)。结论:无管法快速小肠气钡双对比造影法确能形成良好的气钡双对比像,小肠观察效果较口服钡剂法有明显提高;西沙必利较胃复安药效更好、更安全。     

Comparative evaluation of DQ-2511, a novel gastroprokinetic agent,with cisapride in ameliorative action on experimentally induced delayed gastric emptying

We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)-ethyl]carbamoyl]methyl]amino -N- methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ-2511 (3–10 mg kg^?1) caused similar significant improvements to delays in gastric emptying of semi-solid meals evoked by chole-cystokinin-octapeptide (CCK₈: 5 μ kg^?1, i.v.) in monkeys, to that with cisapride (3 mg kg^?1). A 2-week oral treatment of unilaterally vagotomized rats with DQ-2511 (1–10 mg kg^?1) lessened delays in gastric emptying, whereas cisapride (0.3–10 mg kg^?1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 μg kg^?1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ-2511 (6–60 μ kg^?1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric emptying may differ from that of cisapride.     

Cisapride treatment for gastro-oesophageal reflux in children: a systematic review of randomized controlled trials

The aim of the systematic review was to determine the effect of cisapride compared with placebo or other non-surgical therapies for the treatment of symptoms of gastro-oesophageal reflux in children. We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Science Citation Index and reference lists for randomized controlled trials which compared cisapride with placebo or other non-surgical therapy in children. We included only trials which reported reflux-related symptoms as an outcome, provided that cisapride was administered orally for at least I week. Seven trials (286 children in total) compared cisapride with placebo. Two trials reported good concealment of treatment allocation. The pooled odds ratio for the 'same or worse' symptoms was 0.34 (95% CI 0.10, 1.19). There was substantial heterogeneity between studies (P < 0.00001) and the funnel plot was asymmetrical. Adverse effects (mainly diarrhoea) were not significantly increased with cisapride (pooled odds ratio (OR) 1.80: 0.87, 3.70). The reflux index was significantly reduced in children treated with cisapride (weighted mean difference -6.49: -10.13, -2.85). One study (50 children) compared cisapride with gaviscon plus carobel: the OR for the 'same or worse' symptoms was 3.26 (0.93, 11.38). There was no clear evidence that cisapride reduced symptoms of gastro-oesophageal reflux. As smaller, poorer quality studies were biased in favour of a positive treatment effect, the pooled OR overestimated the potential benefits of cisapride. There was some evidence to suggest that gaviscon plus carobel may be a more effective option than cisapride.     

Cisapride and torsades de pointes in a pacemaker patient

Cisapride induced QTprolongation with consequent life-threatening arrhythmias including torsades de pointes has recently been documented but is rare. We report the case of a patient who had received permanent pacemaker therapy for complete AV block with symptomatic bradycardia dependent torsades de pointes, but suffered breakthrough torsades during cisapride therapy despite constant pacing.     

2型糖尿病患者胃排空影响因素及西沙必利治疗观察

[目的]探讨2型糖尿病患者胃排空影响因素、单光子发射计算机断层摄影（SPECT）显影技术和B超在糖尿病性胃轻瘫诊断中的应用及西沙必利治疗效果.[方法]①对120例2型糖尿病进行临床分析.②120例2型糖尿病随机分为两组：A组应用核素^99mTc-SC标记固体试餐,SPECT显像技术检测胃半排空时间（T1/2）;B组予B超检测T1/2.两组均检测空腹血糖（FBG）和糖基化血红蛋白（HbA1c）.③胃T1/2延迟者予西沙必利30 mg,/d,疗程均为1个月,复查胃T1/2.[结果]①糖尿病性胃轻瘫的发生与年龄、病程、空腹血糖、糖基化血红蛋白、神经病变及微血管病变呈正相关（P＜0.01）;②A组60例患者中24例（40.0%）胃T1/2延迟;B组：60例患者中22例（36.7%）.两种检查方法的检出率差异无统计学意义（P＞0.05）;③西沙必利治疗A组有效率为91.7%,B组为90.9%.[结论]糖尿病性胃轻瘫与年龄、病程、高血糖、神经病变及微血管病变相关;SPECT显像技术与B超检出率相似,但不排除与病例数少有关.患者对这两种检查方法耐受性好,但SPECT显像技术费用高,不利于广泛开展,而B超价廉,易于临床使用.西沙必利是有力的促进胃动力的药物,对糖尿病性胃轻瘫有一定的改善胃排空的疗效.     

Evidence of impaired cisapride metabolism in neonates

AIMS: Cisapride has been shown to cause QTc prolongation in neonates in the absence of any of the known risk factors ascribed to children or adults (excessive dosage, drug-drug interactions). Our hypothesis was that the early neonatal liver may show defective elimination of cisapride resulting in its accumulation in the immature child. Owing to the difficulties associated with in vivo pharmacokinetic studies in a paediatric population, we explored the in vitro metabolism of cisapride by human cytochrome P450. METHODS: Experiments were conducted with recombinant CYPs stably expressed in mammalian cells and with liver microsomes obtained from human foetuses, neonates, infants and adults. Cisapride metabolites were measured by high performance liquid chromatography. RESULTS: The rate of biotransformation of cisapride was greater by recombinant CYP3A4 than by CYP3A7 (0.77 +/- 0.5 and 0.01 +/- 0.01 nmol metabolites formed in 24 h, respectively), whereas CYP1A1, 1A2, 2C8, 2C9 and 3A5 showed no activity. Norcisapride formation was significantly correlated with testosterone 6beta-hydroxylation, a CYP3A4 catalysed reaction (r = 0.71, P = 0.03) but not with the 16-hydroxylation of dehydroepiandrosterone, catalysed by CYP3A7 (r = 0.30, P = 0.29) by microsomes from a panel of livers from foetuses, neonates and infants. No or negligible cisapride metabolic activity was observed in microsomes from either foetuses or neonates aged less than 7 days, which contained mostly CYP3A7 and no CYP3A4. The metabolism of cisapride steadily increased after the first week of life in parallel with CYP3A4 activity to reach levels exceeding adult values. CONCLUSIONS: The low content of CYP3A4 in the human neonatal liver appears to be responsible for its inability to oxidize cisapride and could explain its accumulation in plasma leading to the cases of QTc prolongation reported in this paediatric population.