Prucalopride for chronic constipation

Lacy, Brian E.; Loew, Burr J.; Crowell, Michael D.

doi:10.1358/dot.2009.45.12.1423115

Cited by 8 publications

(6 citation statements)

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“…A motilin agonist, ABT‐229, failed to show superiority over placebo in FD . The potent 5HT 4 agonist prucalopride is approved in Europe for chronic constipation but has not been properly evaluated in clinical FD trials . In summary, although prokinetic agents are conceptually appealing given their potential to improve gastric emptying, and are commonly used throughout the world, the results in FD patients are underwhelming.…”

Section: Resultsmentioning

confidence: 99%

Review article: current treatment options and management of functional dyspepsia

Lacy

Talley

Locke

et al. 2012

Aliment Pharmacol Ther

193

143

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SUMMARY Background Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. Aim To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). Results The utility of Helicobacter pylori eradication for the treatment of FD is modest (6–14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7–10% therapeutic gain), histamine-type-2-receptor antagonists (8–35% therapeutic gain), prokinetic agents (18–45%), tricyclic antidepressants (TCA) (response rates of 64–70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. Conclusions A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an antinociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.

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Section: Resultsmentioning

confidence: 99%

Review article: current treatment options and management of functional dyspepsia

Lacy

Talley

Locke

et al. 2012

Aliment Pharmacol Ther

193

143

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“…Moreover, TNX genotype should be evaluated routinely in hEDS patients to better understand its role in specific symptoms, and thus allow targeted treatment of colonic motility (Lacy et al . ) and abdominal nociception (Lyubashina et al . ).…”

Section: Discussionmentioning

confidence: 99%

The extracellular matrix glycoprotein tenascin‐X regulates peripheral sensory and motor neurones

Aktar

Peiris

Fikree

et al. 2018

The Journal of Physiology

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Key points Tenascin‐X (TNX) is an extracellular matrix glycoprotein with anti‐adhesive properties in skin and joints. Here we report the novel finding that TNX is expressed in human and mouse gut tissue where it is exclusive to specific subpopulations of neurones.Our studies with TNX‐deficient mice show impaired defecation and neural control of distal colonic motility that can be rescued with a 5‐HT4 receptor agonist. However, colonic secretion is unchanged. They are also susceptible to internal rectal intussusception. Colonic afferent sensitivity is increased in TNX‐deficient mice. Correspondingly, there is increased density of and sensitivity of putative nociceptive fibres in TNX‐deficient mucosa.A group of TNX‐deficient patients report symptoms highly consistent with those in the mouse model.These findings suggest TNX plays entirely different roles in gut to non‐visceral tissues – firstly a role in enteric motor neurones and secondly a role influencing nociceptive sensory neuronesStudying further the mechanisms by which TNX influences neuronal function will lead to new targets for future treatment. AbstractThe extracellular matrix (ECM) is not only an integral structural molecule, but is also critical for a wide range of cellular functions. The glycoprotein tenascin‐X (TNX) predominates in the ECM of tissues like skin and regulates tissue structure through anti‐adhesive interactions with collagen. Monogenic TNX deficiency causes painful joint hypermobility and skin hyperelasticity, symptoms characteristic of hypermobility Ehlers Danlos syndrome (hEDS). hEDS patients also report consistently increased visceral pain and gastrointestinal (GI) dysfunction. We investigated whether there is a direct link between TNX deficiency and GI pain or motor dysfunction. We set out first to learn where TNX is expressed in human and mouse, then determine how GI function, specifically in the colon, is disordered in TNX‐deficient mice and humans of either sex. In human and mouse tissue, TNX was predominantly associated with cholinergic colonic enteric neurones, which are involved in motor control. TNX was absent from extrinsic nociceptive peptidergic neurones. TNX‐deficient mice had internal rectal prolapse and a loss of distal colonic contractility which could be rescued by prokinetic drug treatment. TNX‐deficient patients reported increased sensory and motor GI symptoms including abdominal pain and constipation compared to controls. Despite absence of TNX from nociceptive colonic neurones, neuronal sprouting and hyper‐responsiveness to colonic distension was observed in the TNX‐deficient mice. We conclude that ECM molecules are not merely support structures but an integral part of the microenvironment particularly for specific populations of colonic motor neurones where TNX exerts functional influences.

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“…The safety and efficacy of prucalopride in CC has been investigated in an extensive development program, 10,13–17 which included three pivotal clinical studies 18–20 . In these randomized, double‐blind, placebo‐controlled studies, adults (18–95 years) with CC received 2 or 4 mg prucalopride tablets once‐daily for 12 weeks.…”

Section: Introductionmentioning

confidence: 99%

“…10 Stimulation of the 5-HT 4 receptor induces facilitation of cholinergic and noncholinergic excitatory neurotransmission, and hence prucalopride has potential for the treatment of disorders associated with small and/or large bowel dysfunction, including constipation, postoperative ileus, and pseudo-obstruction. 11,12 The safety and efficacy of prucalopride in CC has been investigated in an extensive development program, 10,[13][14][15][16][17] which included three pivotal clinical studies. [18][19][20] In these randomized, double-blind, placebo-controlled studies, adults (18-95 years) with CC received 2 or 4 mg prucalopride tablets once-daily for 12 weeks.…”

Section: Introductionmentioning

confidence: 99%

Prucalopride in the treatment of chronic constipation in patients from the Asia‐Pacific region: a randomized, double‐blind, placebo‐controlled study

Zou

Yuan

et al. 2012

Neurogastroenterology Motil

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BackgroundThe study evaluated efficacy and safety of the 2 mg dose of prucalopride compared to placebo in patients with chronic constipation (CC) from the Asia-Pacific region.MethodsRandomized, placebo-controlled, parallel-group, phase III study with 2-week run-in, 12-week treatment phase, and 1-week follow-up. Adult patients with CC (≤2 spontaneous bowel movements per week) received 2 mg prucalopride or placebo, once-daily, for 12 weeks. Primary efficacy measure was percentage of patients with average of ≥3 spontaneous complete bowel movements (SCBMs) per week (Responders) during the 12-week treatment. A key secondary endpoint was Responders during first 4 weeks of treatment. Other efficacy assessments were based on patient diaries, their assessments of symptoms and quality of life, and investigator’s assessment on efficacy of treatment. Safety assessments included adverse events, laboratory values, and cardiovascular events.Key ResultsEfficacy and safety were evaluated for 501 patients who received study drug. On the primary endpoint, prucalopride was significantly more effective than placebo with 83 (33.3%) vs 26 (10.3%) patients having a weekly average of ≥3 SCBMs during the 12-week treatment (P < 0.001). Respective percentages were 34.5%vs 11.1% over first 4 weeks (P < 0.001). On other secondary endpoints, clinical improvement was generally larger and statistically superior (P < 0.001) in the prucalopride group. Most frequently reported adverse events were diarrhea, nausea, abdominal pain, and headache.Conclusion & InferencesPrucalopride 2 mg given once-daily significantly improved bowel function, associated symptoms, and satisfaction in CC over a 12-week treatment period, and was safe and well tolerated by patients in the Asia-Pacific region.

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Prucalopride for chronic constipation

Cited by 8 publications

References 0 publications

Review article: current treatment options and management of functional dyspepsia

Review article: current treatment options and management of functional dyspepsia

The extracellular matrix glycoprotein tenascin‐X regulates peripheral sensory and motor neurones

Prucalopride in the treatment of chronic constipation in patients from the Asia‐Pacific region: a randomized, double‐blind, placebo‐controlled study

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