title: Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis.
abstract: OBJECTIVE
  Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.
  
  
  METHODS
  This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813; and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at the start and end (4 or 12 weeks) of treatment. At these visits, patients assessed the presence and severity of their symptoms.
  
  
  RESULTS
  In total, 280 patients had CTT measurements before and at the end of treatment and were included in the analysis. Their mean age was 43 years, 93% were women, and mean duration of constipation was 19 years. After a once daily treatment with prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95% confidence interval (CI): -18.9, -5.1) and 13.9 h (95% CI: -20.5, -7.4), respectively; CTT increased by 0.5 h (95% CI: -4.5, 5.5) with placebo (n=112). At the end of the trial, symptoms including bloating/flatulence/distension and straining were rated as severe or very severe by a higher proportion of patients with slow or very slow CTT (>48 h) than by those with normal CTT.
  
  
  CONCLUSIONS
  There was a clear relationship between increased CTT and increased symptom severity in patients with chronic constipation. Treatment with prucalopride accelerated CTT in these individuals.
authors.affiliation: GI Physiology Unit, University College London, London, UK.
authors.forename: Anton
authors.initials: A
authors.lastname: Emmanuel
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: Marina
authors.initials: M
authors.lastname: Cools
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Vandeplassche
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: René
authors.initials: R
authors.lastname: Kerstens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001572:Benzofurans / Q000627:therapeutic use*; D002908:Chronic Disease; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003248:Constipation / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058828:Serotonin 5-HT4 Receptor Agonists / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001572:Benzofurans; D058828:Serotonin 5-HT4 Receptor Agonists; C406662:prucalopride
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