The effect of cisapride on defaecation in normal human subjects—lack of effect on faecal excretion of water, fat, and bile acids

In order to elucidate whether or not the increased stool frequency that occurs during cisapride treatment is a result of malabsorption of water, fat, and bile acids, 12 healthy volunteers were dosed with either tablets of placebo q.d.s. or tablets of 10 mg cisapride q.d.s. during two periods of 5 days in a double-blind, crossover study. Stool frequency, stool consistency, and side-effects were recorded each day. Total faecal mass, faecal water content, and faecal excretion of fat and bile acids were determined during the last 72 h of each study period. Mean daily stool frequency was 18.8% higher during cisapride [1.68 +/- 0.12 (S.E.M.)] administration than during placebo (1.42 +/- 0.12); P = 0.038. The stool consistency score increased by 11.8% towards softer stools during cisapride dosing (N.S.). There were no significant differences in total faecal mass (placebo 399.4 g/72 h; cisapride; 414.5 g/72 h), faecal water content (placebo; 75.6%: cisapride 76.2%), or faecal excretion of fat (placebo; 12.7 g/72 h: cisapride; 11.6 g/72 h) and total bile acids (placebo; 2212 mumol/72 h: cisapride; 2261 mumol/72 h). The side-effects reported during placebo were constipation (n = 3), and during cisapride meteorism (n = 4) and increased appetite (n = 2). The increased stool frequency during cisapride treatment is not caused by malabsorption of water, fat, or bile acids, but seems to be the consequence of a direct motor effect.     

The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health

Aliment Pharmacol Ther 2010; 32: 884–893

Summary

Background The short‐term effects of methylnaltrexone (MNTX), a peripherally acting μ‐opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. Aim To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. Methods In a randomized, parallel‐group, double‐blind, placebo‐controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Results Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t_1/2 (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Conclusion Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine‐associated delayed gut transit in health.     

A randomized placebo-controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia

AIM: To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia. METHODS: One hundred and eighty-five patients with functional dyspepsia were randomized and treated in a double-dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent = 0, moderate = 1, severe = 2 or very severe = 3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention-to-treat). RESULTS: At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P = 0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively. CONCLUSIONS: Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment.     

Double-blind study of the effect of cisapride on constipation and abdominal discomfort as components of the irritable bowel syndrome

Aim : To study the effect of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome.
Patients and methods : Ninety-six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study.
Results : After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms ( P <0.05). The corresponding percentages for the placebo-treated patients were 31%, 58% and 19%, respectively, ( P <0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well-being and frequency of stool passage improved significantly within each treatment group ( P <0.05). Evaluation of efficacy parameters using intention-to-treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride ( P 0.05).
Conclusions : These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, hovever, be of use in improving the difficulty of stool passage.     

西沙必利对胆囊切除术后的胃肠蠕动作用

目的 :观察西沙必利对胆囊切除术后胃肠功能恢复的疗效。方法 :采用双盲随机将 12 0例胆囊切除术后的病人分为 2组。西沙必利组 60例 (男性18例 ,女性 4 2例 ,年龄 4 5±s 8a) ,术前 2h用西沙必利 10mg ,po ,术后用 10mg ,po ,q 6h ,直至肛门排气。安慰剂组 60例 (男性 2 2例 ,女性 38例 ,年龄 4 3± 6a) ,服安慰剂 (维生素C) 2片 ,服法与西沙必利组相同。通过询问肛门排气时间来观察疗效。结果 :西沙必利使胆囊切除术后肛门排气时间 (术后13h)较安慰剂组 (术后 39h)明显缩短 (P <0 .0 1)。结论 :西沙必利促进了胆囊切除术后胃肠功能的恢复     

Postoperative ileus: mechanisms and future directions for research

Postoperative ileus (POI) is an abnormal pattern of gastrointestinal motility characterized by nausea, vomiting, abdominal distension and/or delayed passage of flatus or stool, which may occur following surgery. Postoperative ileus slows recovery, increases the risk of developing postoperative complications and confers a significant financial load on healthcare institutions. The aim of the present review is to provide a succinct overview of the clinical features and pathophysiological mechanisms of POI, with final comment on selected directions for future research.Terminology used when describing POI is inconsistent, with little differentiation made between the obligatory period of gut dysfunction seen after surgery (‘normal POI’) and the more clinically and pathologically significant entity of a ‘prolonged POI’. Both normal and prolonged POI represent a fundamentally similar pathophysiological phenomenon. The aetiology of POI is postulated to be multifactorial, with principal mediators being inflammatory cell activation, autonomic dysfunction (both primarily and as part of the surgical stress response), agonism at gut opioid receptors, modulation of gastrointestinal hormone activity and electrolyte derangements. A final common pathway for these effectors is impaired contractility and motility and gut wall oedema. There are many potential directions for future research. In particular, there remains scope to accurately characterize the gastrointestinal dysfunction that underscores an ileus, development of an accurate risk stratification tool will facilitate early implementation of preventive measures and clinical appraisal of novel therapeutic strategies that target individual pathways in the pathogenesis of ileus warrant further investigation.     

Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption

The pharmacokinetic interaction between the gastrointestinal motility-stimulating substance cisapride and the H2-antagonist cimetidine was examined in 8 healthy volunteers (25 +/- 2 years of age). Steady-state kinetics of both substances were investigated after separate 1-week treatments of oral cisapride, 10 mg t.i.d., cimetidine, 400 mg t.i.d., and the two drugs combined. Cimetidine increased the cisapride peak plasma concentration from 58 +/- 25 ng/ml to 84 +/- 19 ng/ml (p = 0.01) and AUC0-24 from 509 +/- 289 ng/ml.h to 738 +/- 148 ng/ml.h (p = 0.02). Cisapride shortened the time to the peak concentration of cimetidine from 1.3 +/- 0.6 h to 0.6 +/- 0.2 h (p = 0.005) and reduced the cimetidine AUC0-24 from 11.0 +/- 2.3 micrograms/ml.h to 9.0 +/- 2.0 micrograms/ml.h (p = 0.05). It is concluded that cimetidine inhibits cisapride metabolism, whereas cisapride enhances the gastrointestinal absorption of cimetidine.     

Gastric myoelectric activity in older adults treated with cisapride for gastro-oesophageal reflux disease

BACKGROUND: The incidence of both gastro-oesophageal reflux disease (GERD) and upper gastrointestinal motility disorders appears to increase with age. However, there is a dearth of data concerning the utility of a prokinetic agent such as cisapride in the treatment of older adults with symptomatic GERD. AIM: To investigate the incidence of electrogastrographic abnormalities in older adults with and without GERD symptoms, as well as the effect of cisapride therapy on symptoms of GERD and electrogastrographic responses. METHODS: We report on 18 older adults with symptomatic GERD and 10 older adult controls (mean ages 71 and 75 years, respectively). Subjects underwent electrogastrographic evaluation pre- and postprandially under baseline conditions and after 1 month of treatment with 10 mg q.d.s. of cisapride. RESULTS: Heartburn frequency and postprandial fullness were both significantly (P < 0. 05) reduced after cisapride treatment. Acid contact time was not significantly changed. The percentage of 2-4 cpm activity in the electrogastrographic analysis was significantly (P < 0.05) increased with cisapride treatment, and the instability coefficient was significantly (P < 0.05) diminished with cisapride treatment. CONCLUSIONS: Enhanced gastric functioning and reduction in heartburn suggest that cisapride is efficacious in the treatment of older adults with symptomatic GERD, and that gastric dysrhythmias and postprandial fullness are resolved with cisapride treatment.     

Adenosine A1 receptor blockade reverses experimental postoperative ileus in rat colon

Inhibition of colonic propulsive motility is the main contributor to postoperative ileus in humans. Experimental models for investigating colonic propulsion in surgically induced postoperative ileus have not previously been available. This study was designed to assess whether adenosine A(1) receptor antagonists (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) reverse the colonic motility disorder in newly developed rat experimental ileus models. When rats underwent anesthesia (pentobarbital) or surgical traumas (partial gastrectomy, cecectomy or gentle touching of the colon with fingers), colonic propulsive motility was evaluated by migration of intracolonically injected dye in awake unrestrained rats. Propulsive motility resulted in significant decrease after the treatment of the anesthesia or partial gastrectomy. Intravenous administration of either adenosine A(1) receptor antagonist reversed the slowed colonic propulsion in these experimental ileus models. The present study suggests that the blockade of adenosine A(1) receptors has therapeutic potential for postoperative ileus.     

小肠内排列术对急性广泛粘连性肠梗阻的临床疗效及其对血清DAO、MDA的影响

目的 探讨小肠内排列术对急性广泛粘连性肠梗阻的临床疗效及其对血清二胺氧化酶(DAO)、丙二醛(MDA)的影响.方法 选取武警后勤学院附属医院于2009年3月-2015年3月收治的120例急性广泛粘连性肠梗阻患者为研究对象.按手术方法分为对照组和观察组各60例,对照组采用传统手术,观察组采用小肠内排列术.观察2组手术前后血清DAO、MDA,胃肠功能恢复时间、术后首次排气时间、腹胀消失时间、住院时间、并发症发生情况等.结果 观察组总有效率高于对照组(P＜0.01).术后2组DAO、MDA均低于术前,且观察组低于对照组(P＜0.01).观察组术后首次排气、腹胀消失、胃肠功能恢复、住院时间均短于对照组,术后并发症发生率低于对照组(P＜0.01).结论 小肠内排列术治疗急性广泛粘连性肠梗阻安全有效,且能够降低血清DAO、MDA含量.     

Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome

BACKGROUND: Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and improves bowel function in non-constipated, female patients with irritable bowel syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption. AIM: To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome. METHODS: A double-blind, placebo-controlled, two-dose study of alosetron was performed in 25 non-constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat. RESULTS: There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo. CONCLUSIONS: Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non-constipated irritable bowel syndrome patients in this study. Alosetron's effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.     

奥曲肽对粘连性肠梗阻患者肠黏膜屏障功能影响及疗效观察

目的：探讨奥曲肽对粘连性肠梗阻患者肠黏膜屏障功能的影响及疗效观察.方法：将80例粘连性肠梗阻患者随机分为奥曲肽组（n=40）和对照组（n=40）.对照组患者予以禁食、胃肠减压、全胃肠外营养和抗炎解痉止痛等基础治疗.奥曲肽组在此基础上加用奥曲肽0.1 mg皮下注射,q8h,至肛门排便排气.观察并比较两组患者治疗前和治疗5d后肠黏膜屏障功能的变化,并进行临床疗效及药物不良反应观察.结果：治疗5d后,两组患者血清内毒素和D-乳酸均明显下降（P＜0.05或0.01）,且奥曲肽组下降幅度明显大于对照组（P＜0.05）;奥曲肽组的临床总有效率为92.5％,明显高于对照组的75.0％（P＜0.05）.两组患者治疗期间均未见明显的药物不良反应.结论：奥曲肽治疗腹部手术后粘连性肠梗阻具有较好的疗效及安全性,能明显改善其临床症状,作用可能与其能降低血清内毒素和D-乳酸水平、保护和改善患者的肠黏膜屏障功能相关.     

The in vivo gastrointestinal activity of TD-5108, a selective 5-HT4 receptor agonist with high intrinsic activity

The in vivo preclinical pharmacodynamic profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity, was compared to that of the clinically studied gastrointestinal pro-kinetic agents, tegaserod, cisapride and mosapride. The activity of TD-5108 was evaluated in guinea pig colonic transit, rat oesophageal relaxation and dog gastrointestinal smooth muscle contractility models. Subcutaneous administration of TD-5108, tegaserod, cisapride and mosapride increased guinea pig colonic transit (rank order of potencies: TD-5108 > tegaserod > cisapride > mosapride). Following intravenous and intraduodenal dosing, TD-5108, tegaserod, cisapride and mosapride produced dose-dependent relaxation of the rat oesophagus. On a molar basis, TD-5108 was approximately twofold less potent than tegaserod following intravenous dosing but 6- or 86-fold more potent than cisapride or mosapride, respectively, and 9- or 18-fold more potent than tegaserod or cisapride, respectively, after intraduodenal administration. Orally dosed TD-5108 increased the contractility of the canine antrum, duodenum and jejunum with higher potency than tegaserod. The selective 5-HT(4) receptor agonist, TD-5108, demonstrates robust in vivo activity in the guinea pig, rat and dog gastrointestinal tracts.     

Postoperative ileus: progress towards effective management

The pathogenesis of postoperative ileus (PI) is multifactorial, and includes activation of inhibitory reflexes, inflammatory mediators and opioids (endogenous and exogenous). Accordingly, various strategies have been employed to prevent PI. As single-modality treatment, continuous postoperative epidural analgesia including local anaesthetics has been most effective in the prevention of PI. Choice of anaesthetic technique has no major impact on PI. Minimally invasive surgery reduces PI, in accordance with the sustained reduction in the inflammatory responses, while the effects of early institution of oral nutrition on PI per se are minor. Several pharmacological agents have been employed to resolve PI (propranolol, dihydroergotamine, neostigmine, erythromycin, cisapride, metoclopramide, cholecystokinin, ceruletide and vasopressin), most with either limited effect or limited applicability because of adverse effects. The development of new peripheral selective opioid antagonists is promising and has been demonstrated to shorten PI significantly. A multi-modal rehabilitation programme including continuous epidural analgesia with local anaesthetics, enforced nutrition and mobilisation may reduce PI to 1-2 days after colonic surgery.     

埃索美拉唑静脉滴注治疗非静脉曲张性上消化道出血的疗效观察

目的：评估埃索美拉唑40mg静脉注射治疗急性非静脉曲张性上消化道出血的疗效和安全。方法：对内镜证实的25例急性非静脉曲张性上消化道出血征象的患者，随机、双盲分为埃索关拉唑组（n=19）和奥美拉唑组（n=6），实验组和对照组分别给予埃索美拉唑和奥美拉唑40mg q12h静脉滴注，治疗5d。观察72h及120h的临床止血疗效及药物不良事件。结果：治疗72h两组临床上无消化道出血征象受试者百分率无显著性差异（P〉0．05）。治疗120h有效率两组均为100％。中位止血时间埃索关拉唑组为41h，奥美拉唑组为20h，两组比较无显著性差异（P〉0．05）。不良事件发生情况两组相似，均无与药物有关的严重不良事件发生。结论：静脉给予埃索美拉唑治疗急性非静脉曲张性上消化道出血疗效不劣于奥美拉唑，和奥美拉唑相比也有很好的耐受性。     

门奇静脉断流改良术治疗门静脉高压症上消化道出血的效果评价

目的 探讨门奇静脉断流改良术治疗门静脉高压症上消化道出血的效果,为临床选择术式提供参考.方法 选取2006年6月～2012年6月140例门静脉高压症上消化道出血患者,按随机数字表法分为普通组和治疗组,各70例,普通组实施传统门奇静脉断流术治疗,治疗组实施门奇静脉断流改良术（即贲门周围血管离断加胃底环缝扎手术）治疗,术后对比两组的肝功能指标及手术指标.结果 两组治疗前后及治疗后的肝功能指标比较差异均无统计学意义（P＞0.05）.治疗组术后并发症发生率为10.00％,普通组为12.86％,差异无统计学意义（χ2=1.024,P=0.219）.治疗组住院时间为（12.93±4.04）d,普通组为（17.29±4.34）d,差异有统计学意义（t=5.394,P=0.016）.治疗组上消化道再出血发生率为1.43％,普通组为12.86％,差异有统计学意义（χ2=-1 3.445,P=0.001）.结论 门奇静脉断流改良术治疗门静脉高压症上消化道出血的临床效果显著,临床上可优先选用此术式.     

The effect of a single rectal dose of cisapride on delayed gastric emptying

Background : Cisapride has an established prokinetic effect in patients with delayed gastric emptying. However, rectal administration of the drug might be preferred in patients with either dysphagia or nausea due to gastroparesis.
Aim : To determine the effect of a single rectal dose of cisapride 60 mg on gastric emptying in patients with delayed gastric emptying.
Methods : Thirty-two patients (16 males, 16 females) with demonstrated delayed gastric emptying received a single dose of two suppositories containing either cisapride (2 × 30 mg) or placebo, according to a double-blind randomized crossover design. Three hours after administration of the suppositories, the patients received a radio-labelled test meal and radio-opaque markers for measurement of gastric emptying.
Results : The mean t _½ after cisapride administration (76 min, 95% CI: 68–95) was significantly shorter ( P  = 0.005; n  = 28, per-protocol analysis) than after placebo administration (104 min, 81–126). Four hours after ingestion of the meal significantly fewer radio-opaque markers remained in the stomach after cisapride than after placebo administration ( P  < 0.05). Mild to moderate adverse events, mainly involving the gastrointestinal tract, were reported in 10 patients (31%) after cisapride treatment and in four patients (13%) after placebo (N.S.; n  = 32).
Conclusion : A single suppository dose of cisapride 60 mg significantly accelerates gastric emptying of the solid phase of a meal and of radio-opaque markers in patients with previously demonstrated delayed gastric emptying.     

泮托拉唑钠治疗急性上消化道出血21例

目的：观察泮托拉唑钠治疗急性上消化道出血的疗效及安全性。方法：将42例患分为2组，治疗组(泮托拉唑钠)2l例，静脉滴注泮托拉唑钠40mg，2次／d，疗程3—5d；对照组(奥美拉唑钠)2l例，静脉滴注奥美拉唑钠40mg，2次／d，疗程3-5d.结果：治疗3d后，泮托拉唑治疗组总有效率为94．4％，患疼痛、呕血、黑便等症状消失率分别为93．7％，100．0％和90.5％，与对照组比较疗效无显性差异，且治疗组用药期间未发现严重不良反应。结论：泮托拉唑治疗急性上消化道出血安全、有效。     

Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers

BACKGROUND: Alosetron is a 5-hydroxytryptamine-3 receptor antagonist reducing symptoms in female patients with diarrhoea-predominant irritable bowel syndrome, and is known to increase the colonic transit time. AIM: To study the effect of alosetron on left colonic phasic motility in ambulant non-constipated patients with irritable bowel syndrome and healthy volunteers. METHODS: In a double-blind, randomized, crossover design, 10 patients with irritable bowel syndrome and 12 sex- and age-matched volunteers were treated for two 7-day periods with alosetron, 4 mg b.d., or placebo b.d. On day 6 of each treatment period, a six-channel solid-state manometric catheter was positioned in the left colon and 24 h motility was studied on day 7. The periprandial phasic motility around dinnertime was evaluated in the descending and sigmoid colon. The high-amplitude propagated contraction frequency and characteristics were calculated. RESULTS: Alosetron appeared to increase the overall periprandial frequency in the sigmoid colon (P=0.043) and the mean amplitude of colonic contractions in the descending colon (P=0.007). The high-amplitude propagated contraction frequency was higher on alosetron during the second half of the day for patients with irritable bowel syndrome (P=0.002), with increased mean propagation length of high-amplitude propagated contractions (P=0.001). The stool frequency (P=0.024) and stool consistency score (P=0.002) were decreased by alosetron. CONCLUSIONS: The 5-hydroxytryptamine-3 receptor antagonist alosetron marginally increased left colonic periprandial phasic motility. Alosetron increased the number and propagation length of high-amplitude propagated contractions, which were paradoxically accompanied by a decrease in stool frequency and a firming of stool consistency.     

Cisapride 20 mg b.d. for preventing symptoms of GERD induced by a provocative meal

BACKGROUND: Cisapride is a substituted piperidinyl benzamide indicated for the symptomatic treatment of patients with nocturnal heartburn due to gastro-oesophageal reflux disease (GERD). The currently recommended dosing regimen for cisapride is 10 mg q.d.s., but the elimination half-life of 8-10 h supports b.d. dosing with 20 mg. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial was undertaken to determine the efficacy and safety of cisapride 20 mg b.d. dosing in reducing or preventing heartburn and other meal-related symptoms after challenge with a provocative fatty meal. In phase 1 of the study, 137 patients with at least a 3-month history of symptoms suggestive of GERD and at least five episodes of GERD on 7-day diary were eligible to receive single-blind treatment with placebo for 7 (range +/- 3) days and then ingested a provocative meal. One hundred and twenty-two patients (45 men and 77 women, 22-65 years of age) who experienced heartburn during the 3 h after ingestion of the meal qualified for the double-blind phase of the study and were randomly assigned to either cisapride 20 mg or matching placebo b.d. for 7 (+/-3) days. At the end of this period, 118 patients again ate a fatty meal and were assessed for symptoms of GERD. RESULTS: Heartburn was prevented in a significantly higher percentage of cisapride-treated patients (40%; 24 out of 60) than placebo-treated patients (21%; 12 out of 58) after the repeat provocative meal at the end of the double-blind phase (P = 0.017). Cisapride was also significantly more effective in reducing the severity of postprandial heartburn, belching, and regurgitation (P < 0.05). Twice-daily dosing with cisapride 20 mg was well tolerated; the number of cisapride- and placebo-treated patients who experienced at least one adverse event was similar (31% and 22%, respectively). The most common adverse events were diarrhoea (cisapride, 18%; placebo, 0%) and rhinitis (cisapride, 2%; placebo, 5%). CONCLUSIONS: These results demonstrate that cisapride 20 mg b.d. is effective in preventing or reducing symptoms of heartburn in patients who developed heartburn after ingesting a provocative fatty meal. Cisapride was also effective in reducing the severity of heartburn-related symptoms such as belching and regurgitation.