Reporte de un caso de tratamiento de gastroparesia pediátrica con prucaloprida: una terapia novedosa / A case report of prucalopride treatment in pediatric gastroparesis: a novel therapy

La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.

Prucalopride: novel drug for chronic idiopathic constipation

Chronic Idiopathic Constipation (CIC), defined as constipation in which the underlying cause is unknown, is a common medical illness with a profound negative impact on health-related quality of life and increased propensity for life threatening complications. Current treatment for CIC includes lifestyle modifications, over-the-counter medications, and prescription medications. Presently, the only approved, prescription products for CIC in the US are prosecretory agents. However, the current knowledge that serotonin plays an important role in colonic motility has opened new horizons in the treatment of CIC promoting use of prokinetic agents with a different mechanism of action. Prucalopride is a highly selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist that enhances propulsive motor patterns in the large intestine due to a high affinity for 5-HT4 receptors in gastrointestinal (GI) tissues. The onset of action of Prucalopride is fast, shows rapid absorption, oral bioavailability of 93% and linear pharmacokinetics. Most common adverse reactions seen are headache, nausea, diarrhea, and abdominal pain. Clinical trials for Prucalopride have been positive, and results suggest that the drug may be a new safe and effective option for CIC treatment, especially for patient’s refractory to prosecretory agents. As a prescription drug for the management of constipation and given the virtual demise of other prokinetic agents for this indication, prucalopride competes primarily with another class of agents: those that stimulate secretion. With Shire Pharmaceuticals having already received US FDA approval in Dec 2018, Prucalopride may soon be a new addition to the mounting armoury of drugs against CIC.

Current developments in pharmacological therapeutics for chronic constipation

Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.

Effect of Prucalopride in the Treatment of Chronic Constipation in Asian and Non-Asian Women: A Pooled Analysis of 4 Randomized, Placebo-controlled Studies

BACKGROUND/AIMS: To compare the efficacy and safety of prucalopride, a novel selective high-affinity 5-hydroxytryptamine type 4 receptor agonist, versus placebo, in Asian and non-Asian women with chronic constipation (CC). METHODS: Data of patients with CC, receiving once-daily prucalopride 2-mg or placebo for 12-weeks, were pooled from 4 double-blind, randomized, phase-III trials (NCT00488137, NCT00483886, NCT00485940 and NCT01116206). The efficacy endpoints were: average of > or = 3 spontaneous complete bowel movements (SCBMs)/week; average increases of > or = 1 SCBMs/week; and change from baseline in each CC-associated symptom scores (bloating, abdominal pain, hard stool and straining). RESULTS: Overall, 1,596 women (Asian [26.6%], non-Asian [73.4%]) were included in this analysis. Significantly more patients in the prucalopride group versus placebo experienced an average of > or = 3 SCBMs/week in Asian (34% vs. 11%, P or = 1 SCBMs/week from baseline was significantly higher in the prucalopride group versus placebo among both Asian (57.4% vs. 28.3%, P < 0.001) and non-Asian (45.3% vs. 24.0%, P < 0.001) subgroups. The difference between the subgroups was not statistically significant. Prucalopride significantly reduced the symptom scores for bloating, hard stool, and straining in both subgroups. CONCLUSIONS: Prucalopride 2-mg once-daily treatment over 12-weeks was more efficacious than placebo in promoting SCBMs and improvement of CC-associated symptoms in Asian and non-Asian women, and was found to be safe and well-tolerated. There were numeric differences between Asian and non-Asian patients on efficacy and treatment emergent adverse events, which may be partially due to the overlap with functional gastrointestinal disorders in non-Asian patients.

Effects of Mosapride on capsule endoscopy in elderly patients / 中华老年医学杂志

Objective To explore the effect of oral mosapride on gastrointestinal transit time in elderly patients undergoing capsule endoscopy.Methods A total of 61 patients referred for capsule endoscopy during 2010 September to 2012 January were involved in this study.40 patients over 65 years old were prospectively randomized into mosapride citrate group (n=19) or non-mosapride citrate group (n=21).Patients under 65 years old were in control group (n=21).Mosapride citrate group took 10 mg mosapride citrate orally before endoscopy.The gastrointestinal transit time was calculated.Results Gastric emptying time and small intestinal transit time of patients over 65 years old were significantly shorter in mosapride citrate group than in non-mosapride citrate group [(48.6± 21.1) minand (64.3±22.4) min,t=2.274,P=0.029; (302.2±67.6) min vs.(347.14±51.18) min,t=2.384,P=0.022].There were on significant differences in gastric emptying time and small intestinal transit time between non-older group [(45.4 ± 28.4) min and (284.8 ± 78.3) min] and mosapride citrate group (t=0.407,P=0.686;t=0.751,P=0.457).There was a difference in the image score between medication group and no medication group (4.94±0.63 versus 4.50±0.68; t=2.137,P=0.039) in over 65 years old patients.Conclusions Mosapride may decreased the gastric emptying time and small intestinal transit time,improves the capsules endoscopy image quality and testing completion rate.

The Effects of Prucalopride on Postoperative Ileus in Guinea Pigs

PURPOSE: Postoperative ileus (POI) is an impairment of coordinated gastrointestinal (GI) motility that develops as a consequence of abdominal surgery and is a major factor contributing to patient morbidity and prolonged hospitalization. The aim of this study was to investigate the effects of different 5-hydroxytryptamine 4 (5-HT4) receptor agonists, which stimulate excitatory pathways, on a POI model. MATERIALS AND METHODS: The experimental model of POI in guinea pigs was created by laparotomy, gentle manipulation of the cecum for 60 seconds, and closure by suture, all under anesthesia. Different degrees of restoration of GI transit were measured by the migration of charcoal. Colonic transit was indirectly assessed via measurement of fecal pellet output every hour for 5 hours after administration of various doses of mosapride, tegaserod, prucalopride, and 5-HT. RESULTS: Charcoal transit assay showed that various 5-HT4 receptor agonists can accelerate delayed upper GI transit in a dose-dependent manner. However, fecal pellet output assay suggested that only prucalopride had a significant effect in accelerating colonic motility in POI. CONCLUSION: Although mosapride, tegaserod, and prucalopride produce beneficial effects to hasten upper GI transit in the POI model, prucalopride administered orally restores lower GI transit as well as upper GI transit after operation in a conscious guinea pig. This drug may serve as a useful candidate for examination in a clinical trial for POI.

Plasticity of 5-HT receptors in the IBS subgroups of experimental rats / 西安交通大学学报(医学版)

Objective To investigate the effect of 5-hydroxytryptamine(5-HT) and the plasticity of 5-HT3 and 5-HT4 receptors in the myenteric plexus on the pathogenesis of irritable bowel syndrome(IBS) subgroups.Methods Twenty-seven male rats were randomly divided into three groups: IBS with diarrhea(IBS-D) group,IBS with constipation(IBS-C) group and blank control group.IBS-D model was made in rats by intracolonic instillation with acetic acid.IBS-C model was made in rats by gastric instillation with cool water.After rats in each group were killed,a colon segment was removed for detecting enteric neuron and excitatory neurotransmitter in the myenteric plexus using 5-HT and 5-HT3,5-HT4 receptors immunohistochemistry method.Results ① The number of 5-HT positive neurons in the myenteric plexus of IBS-D group(4.37?0.88) group was significantly higher than that in control group(2.99?0.41,P0.05).② The results of the experiment showed that there was no difference in the number of 5-HT3 receptor positive neurons in the myenteric plexus among each group(F=0.082,P=0.922).③ The positive value of 5-HT4 receptor immunoreactive neurons in the myenteric plexus of IBS-D group(141.98?6.96) group was significantly higher than that in control group(159.90?2.55)(P0.05).Conclusion Increased number of 5-HT and 5-HT4 receptor positive neurons in the myenteric plexus may be related to the pathogenesis of IBS-D rat model.