西沙必利治疗非溃疡性消化不良

目的：验证西沙必利（ｃｉｓａｐｒｉｄｅ）对非溃疡性消化不良的疗效。方法：采用双盲随机将８６例非溃疡性消化不良病人分为２组。西沙必利组４６例（男性３３例，女性１３例；年龄３６±ｓ８ａ），用西沙必利５ｍｇ，ｐｏ，ｔｉｄ；安慰剂组４０例（男性２９例，女性１１例；年龄３４±１０ａ），用安慰剂１片，ｐｏ，ｔｉｄ，２组均４ｗｋ为一个疗程。治疗后１～４ｗｋ通过直接提问来评价２组病人症状改善情况。结果：西沙必利对非溃疡性消化不良的症状改善率和症状严重程度的改善皆较安慰剂组有明显的效果（Ｐ＜０．０１）。结论：西沙必利对治疗非溃疡性消化不良有效。     

Cisapride-Induced Torsades de Pointes

Cisapride-Induced Torsades de Pointes. Two cases of torsades de pointes associated with cisapride are presented, both in association with concomitant drug therapy that inhibits cisapride biotransformation. In one case, plasma cisapride was elevated days after the event, strongly supporting a role for accumulation of the drug in causing the arrhythmia. It is emphasized that these adverse drug reactions are not idiosyncratic, hut rather are predictable based on an understanding of the underlying mechanisms.     

Slow gastric emptying induced by high fat content of meal accelerated by cisapride administered rectally

The evaluation of agents potentially accelerating gastric emptying in gastric stasis syndromes is time-consuming. Since a previous study showed that emptying is slowed after antecedent fat ingestion and intravenous cisapride abolishes this effect, we investigated whether emptying delayed by fat incorporated into a meal is reversed by cisapride and thus could serve as a model for such evaluations. Twelve healthy males received, under double-blind conditions, 30 mg cisapride rectally or placebo, and 3 hr thereafter a semisolid meal of low (9.2 g) or high (37.9 g) fat content. The sequence of combinations placebo/low-fat meal, placebo/high-fat meal, and cisapride/high-fat meal was randomized. Gastric emptying and antral motility were recorded scintigraphically. After placebo/high-fat, emptying was significantly slower (P<0.05) than after placebo/low-fat. After cisapride/high-fat, emptying was significantly faster (P<0.01) than after placebo/high-fat and similar to that after placebo/low-fat. Antral motility was little affected. The slow emptying of a high-fat meal thus seems a suitable model for the evaluation of prokinetic drug effects.     

西沙必利对地高辛的药物动力学影响

本文采用荧光偏振免疫法（ＦＰＩＡ），通过对６只家兔体内地高辛血药浓度的测定，研究西沙必利对地高辛药动学参数的影响，结果表明，西沙必利可影响地高辛的清除半衰期（Ｔ１／２）、消除速率常数（Ｋｅ）、清除率（Ｑ／Ｆ）和药时曲线下面积（ＡＵＣ），提示临床合用西沙必利和地高辛时，应酌情增量，并加强血药浓度的监测。     

Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placebo

BACKGROUND AND AIM: Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome (IBS). To gain further evidence, this randomized double-blind study was carried out. METHODS: Eighty-two symptomatic outpatients were randomized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks. In patients without satisfactory improvement after 4 weeks, the dose was doubled. Symptom evaluation used visual analog scales (VAS) and the investigators' global assessment. RESULTS: After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo patients the dose was doubled because of insufficient improvement of symptoms. The mean VAS score for patients' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of therapy as good or excellent in 70% of the cisapride and 50% of the placebo group. Neither these nor further efficacy parameter differences reached statistical significance. CONCLUSIONS: These results indicate that the effect of 15-30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo. During the 12 week treatment of this trial cisapride proved to be safe and tolerable.     

Effects of cisapride on QTc interval in neonates

AIM—Prospective survey of the effects of cisapride on QTc interval in neonates given cisapride.METHODS—QTc interval was determined just before and 2.9 (0.9) days after outset of the treatment in 49 neonates treated with cisapride between 1 August 1995 and 29 February 1996.RESULTS—Cisapride significantly increased QTc interval (p = 0.0001), and this was higher when birthweight or gestational age were lower. The prolongation of QTc interval above the arbitrary value of 0.450 (n = 7) was clinically asymptomatic and was significantly more common in the infants born with a gestational age ? 33 weeks (n = 6).CONCLUSION—The findings indicate that cisapride accumulates in less mature neonates. Further pharmacokinetic studies are needed.     

西沙必利与其他药物的相互作用

目的 了解促胃肠动力药西沙必利与其他药物合用时的相互作用。方法 通过对近期文献的阅读、分析和归纳，加以综述。结果 西沙必利由细胞色素P—450(CYP)3A4代谢，有较强的首过效应，所以许多CYP3A4底物或(和)抑制剂都能抑制西沙必利的代谢，使其血药浓度升高，从而可能引起心脏QT间期延长、心律失常，甚至导致扭转型室速(TdP)。药效学研究表明，西沙必利与可以引起QT间期延长的药物合用后，也可能增加心脏的毒性反应。结论 西沙必利应避免与CYP3A4抑制刑、CYP3A4底物及易引起QT间期延长的药物合用。如果必需合用，应密切观察合用后的情况，并进行心电监护或血药浓度的监测，以保证临床用药的安全有效。     

曲美布汀治疗功能性消化不良

目的 :比较曲美布汀与西沙必利、甲氧氯普胺治疗功能性消化不良的疗效及安全性。方法 :将2 80例功能性消化不良病人随机分为 3组 ,曲美布汀组 1 0 0例 [男性 3 9例 ,女性 61例 ,年龄 (4 1±s 1 4)a]给曲美布汀 2 0 0mg,po,tid;西沙必利组 90例 [男性 3 1例 ,女性 5 9例 ,年龄 (4 2± 1 3 )a]给西沙必利 1 0mg,po,tid ;甲氧氯普胺组 90例 [男性 3 0例 ,女性 60例 ,年龄 (4 3± 1 1 )a]给甲氧氯普氨1 0mg,po,tid。疗程均为2wk。结果 :总有效率曲美布汀组 85 % ,西沙必利组为 84% ,甲氧氯普胺组为 62 % ,经Ridit分析 ,曲美布汀、西沙必利 2组疗效差异无显著意义 (P >0 .0 5 ) ,曲美布汀、甲氧氯普胺 2组疗效差异有非常显著意义 (P <0 .0 1 )。不良反应曲美布汀、西沙必利 2组相近 ,曲美布汀组明显少于甲氧氯普胺组 (P <0 .0 5 )。结论 :曲美布汀治疗功能性消化不良近期疗效显著、安全 ,与西沙必利相近 ,优于甲氧氯普胺     

Diagnosis and treatment of gastro-oesophageal reflux disease in infants and children

Gastro-oesophageal reflux is a frequent, aspecific phenomenon in infants and children. The recommended approach in infants with uncomplicated regurgitation consists of reassurance of the parents and, if this fails, dietary recommendations in formula-fed infants. If, despite these efforts, symptoms persist, administration of prokinetics, such as cisapride, is recommended prior to investigations such as oesophageal pH monitoring. Oesophageal pH monitoring is also recommended to document gastro-oesophageal reflux disease in children with unusual presentations such as chronic respiratory disease. Today, cisapride is the drug of choice because it has the best efficacy and safety profile. In infants and children presenting with symptoms suggesting oesophagitis, endoscopy of the upper gastrointestinal tract is recommended. If there is severe oesophagitis, acid suppression with histamine H2-receptor antagonists or proton pump inhibitors in combination with prokinetics, are recommended. In life-threatening situations, or in patients that are resistant to or dependent on acid-suppressive medication, a surgical procedure such as laparascopic Nissen procedure should be considered.