The efficacy of a 40-mg extended-release formulation of cisapride in the treatment of patients with gastro-oesophageal reflux.
ABSTRACT This study was conducted to assess the efficacy of a novel 40-mg extended-release formulation of cisapride in reducing gastro-oesophageal reflux.
According to a double-blind, randomized, placebo-controlled design, 19 patients with pathological gastro-oesophageal reflux were treated with extended (40 mg o.d.) or immediate (10 mg q.d.s.) release formulations for two periods of 4 days each (pH-monitoring on day four). Patients received identical treatments in both periods to allow limits of agreement defining equivalent potency of both formulations to be derived from intra-individual variability of treatment effects.
The extended-release formulation decreased total and upright reflux times by 5.5 +/- 1.3% and 8.1 +/- 2.1% (P < 0.001), respectively. It did not change the percentage supine reflux time but diminished the mean duration of reflux episodes by 1.0 +/- 0.4 min (P=0.005). The total number of reflux episodes remained unaltered with both formulations. Immediately-released cisapride decreased total, upright, and supine acid exposures by 5.8 +/- 1.3%, 6.8 +/- 1.6% (P < 0.002) and 3.6 +/- 1.8%, respectively, and mean duration of episodes by 0.9 +/- 0.2 min (P </= 0.05). Equivalent potency for both formulations was accepted in terms of percentage total and upright acid exposure and mean duration of episodes.
The 40-mg extended-release formulation of cisapride decreases total acid exposure and in this study is equivalent to the conventional immediate-release 10 mg q.d.s. regimen. Cisapride primarily interferes with reflux by improving oesophageal acid clearance.
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ABSTRACT: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.Alimentary Pharmacology & Therapeutics 02/2012; 35(7):745-67. · 4.55 Impact Factor
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ABSTRACT: To evaluate the efficiency by which the 5-HT4 agonist cisapride affects important motor functions involved in the control of gastro-oesophageal reflux. Thirty patients with proven gastro-oesophageal reflux disease (endoscopy and 24 h pH-metry) were included in a randomized, double-blind, placebo controlled study with a cross-over design. Cisapride, 20 mg b.i.d., during 4 weeks was compared with placebo. At baseline, as well as after 4 and 8 weeks all patients underwent symptom assessments, sleeve manometry with concomitant oesophageal pH-monitoring and an acid clearance test. Despite adequate plasma levels cisapride had no significant effect on swallow induced peristaltic amplitude, duration, propagation speed, the elicitation of secondary peristalsis nor on acid clearance. Neither the basal tone of the lower oesophageal sphincter nor the number of transient lower oesophageal sphincter relaxations induced by gas distension of the stomach was affected by the administered dose of cisapride. Although cisapride has been alleged to improve symptoms as well as the oesophagitis in patients with gastro-oesophageal reflux disease, we found the compound (20 mg b.i.d.) devoid of effects on important motor mechanisms involved in the pathogenesis of the disease.European Journal of Gastroenterology & Hepatology 02/2002; 14(1):9-14. · 1.92 Impact Factor
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ABSTRACT: Cisapride, the prototype serotonergic agent, evolved from a body of research that defined the key roles of serotonergic receptors in gastrointestinal motor and sensory function. Impressed by its in vitro properties and encouraged by clinical trial data, cisapride became the drug of choice for the treatment of a wide range of motility disorders and clinicians appeared impressed by its efficacy and comfortable with its side-effect profile. Once serious cardiac events began to be reported in association with cisapride therapy, dark clouds rapidly gathered and soon enveloped the drug, leading to its widespread withdrawal from markets. What lessons can we learn from the story of cisapride? How can its brief but spectacular rise and equally sensational demise inform the development of new drugs which are so sorely needed in the management of motility and functional gastrointestinal disorders? This review explores the background to the development of cisapride, its history in clinical trials and the experience with adverse events and, in so doing, attempts to identify lessons for the future in the therapeutics of enteric neuromodulatory drugs.Journal of Digestive Diseases 06/2011; 12(3):147-56. · 1.85 Impact Factor