prucalopride and Fecal-Incontinence

Conservative treatment of fecal incontinence and obstructive defecation can be treated by many conservative treatment modalities. This article presents the options of medication therapy, spincter exercises, electric stimulation, transcutaneous tibial nerve stimulation, anal irrigation and injection of bulking agents. These methods are presented with reference to the currently available literature but the evidence-based data level for all methods is low. For minor disorders of anorectal function these conservative methods can lead to an improvement of anorectal function and should be individually adapted.

Topics: Anal Canal; Antidiarrheals; Benzofurans; Combined Modality Therapy; Electric Stimulation Therapy; Evidence-Based Medicine; Fecal Incontinence; Female; Humans; Intestinal Obstruction; Loperamide; Male; Pelvic Floor Disorders; Physical Therapy Modalities; Polyethylene Glycols; Randomized Controlled Trials as Topic; Serotonin 5-HT4 Receptor Agonists; Surface-Active Agents; Transcutaneous Electric Nerve Stimulation

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.. 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).. 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.. 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.

Topics: Administration, Oral; Area Under Curve; Benzofurans; Child; Child, Preschool; Constipation; Defecation; Fecal Incontinence; Feces; Female; Gastrointestinal Motility; Humans; Laxatives; Male; Serotonin 5-HT4 Receptor Agonists; Tablets; Treatment Outcome