title: Oral prucalopride in children with functional constipation.
abstract: OBJECTIVE
  Prucalopride is a selective, high-affinity 5-HT4 receptor agonist with gastrointestinal prokinetic activities. The aim of this study was to evaluate the pharmacokinetics, efficacy, safety, and tolerability of prucalopride oral solution in children, ages 4 years or older to 12 years or younger, with functional constipation.
  
  
  METHODS
  A single oral dose of 0.03 mg/kg prucalopride was administered to 38 children to characterize prucalopride pharmacokinetics (NCT01674166). Thereafter, 37 children entered an open-label extension period in which 0.01 to 0.03 mg/kg of prucalopride was administered once per day for 8 weeks to investigate efficacy, safety, and tolerability (NCT01670669).
  
  
  RESULTS
  Mean (standard deviation [SD]) Cmax, tmax, and AUC∞ (area under the plasma concentration-time curve from time 0 to infinity) were 3.8 (0.6) ng/mL, 1.8 (0.9) hour, and 65.3 (10.6) ng · h · mL, respectively, with limited (16%) variability in Cmax and AUC∞. Mean (SD) t1/2 was 19.0 (3.1) hours. On average, mean (SD) renal clearance (0.25 [0.08] L · h · kg) accounted for 54% of the apparent total plasma clearance (0.46 [0.07] L · h · kg). The apparent volume of distribution was 12.6 (2.6) L/kg. Prucalopride treatment resulted in a mean bowel movement frequency of 6.8/week, normal stool consistency, and reduced frequency of fecal incontinence. During the 8-week extension, 70% of study participants had at least 1 adverse event (all but 1 of mild/moderate intensity, 19% considered related to prucalopride). No children discontinued prucalopride because of adverse events.
  
  
  CONCLUSIONS
  The pharmacokinetic profile of a single dose of prucalopride oral solution (0.03 mg · kg · day) generally resembled the profile in adults (2-mg tablet) but reflected lower systemic exposure in children. Prucalopride treatment for 8 weeks demonstrated an apparent favorable efficacy and tolerability profile in children with functional constipation.
authors.affiliation: MassGeneral Hospital for Children, Boston, MA 02114, USA. hwinter@partners.org
authors.forename: Harland S
authors.initials: HS
authors.lastname: Winter
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Lorenzo
authors.forename: Marc A
authors.initials: MA
authors.lastname: Benninga
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gilger
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
authors.forename: Paul E
authors.initials: PE
authors.lastname: Hyman
authors.forename: Lieve
authors.initials: L
authors.lastname: Vandeplassche
authors.forename: Jannie
authors.initials: J
authors.lastname: Ausma
authors.forename: Mieke
authors.initials: M
authors.lastname: Hoppenbrouwers
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D001572:Benzofurans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000188:drug therapy*; D003672:Defecation / Q000187:drug effects*; D005242:Fecal Incontinence / Q000188:drug therapy; D005243:Feces; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D054368:Laxatives / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D058828:Serotonin 5-HT4 Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013607:Tablets; D016896:Treatment Outcome
chemical_list: D001572:Benzofurans; D054368:Laxatives; D058828:Serotonin 5-HT4 Receptor Agonists; D013607:Tablets; C406662:prucalopride