Skip Navigation LinksHome > August 2013 - Volume 57 - Issue 2 > Oral Prucalopride in Children With Functional Constipation
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318292f9ea
Original Articles: Gastroenterology

Oral Prucalopride in Children With Functional Constipation

Winter, Harland S.*; Di Lorenzo, Carlo; Benninga, Marc A.; Gilger, Mark A.§; Kearns, Gregory L.||; Hyman, Paul E.; Vandeplassche, Lieve#; Ausma, Jannie#; Hoppenbrouwers, Mieke#

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Abstract

Background and Objectives: 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−1 · mL−1, 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−1 · kg−1) accounted for 54% of the apparent total plasma clearance (0.46 [0.07] L · h−1 · kg−1). 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−1 · day−1) 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.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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