benzofurans 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

To evaluate change in fecal incontinence symptom severity after 8 weeks of darifenacin therapy in patients with double incontinence-urgency urinary incontinence (UUI) and fecal incontinence. Important secondary outcomes included fecal incontinence symptom distress and impact on quality of life, fecal incontinence episodes, global impression of improvement and overactive bladder symptom distress and impact.. Prospective open-label cohort study of women presenting primarily with UUI, diagnosed with double incontinence and electing antimuscarinic therapy for UUI. Women ≥ 18 years with moderate or greater bothersome UUI and fecal incontinence of liquid/solid stool with St. Marks (Vaizey) score ≥ 12 were included. Subjects were treated with darifenacin 15 mg daily for 8 weeks. The primary outcome was change in fecal incontinence symptom severity using the St. Marks (Vaizey) score after 8 weeks. Sample size was based on the minimally important difference of the St. Marks, -5, and standard deviation, ± 8.5; 30 subjects provided 80% power and type I error of 0.05, including a 15% attrition rate.. Thirty-two women were consented with mean baseline St. Marks (Vaizey) score of 18.0 ± 3.0. Mean age was 66.5 ± 10.3 years. Twenty-eight subjects (29/32, 87.5%) completed assessments. St. Marks (Vaizey) score significantly improved from 18.0 to 11.0 [mean difference - 7.0, 95% confidence interval (CI): -8.7, -5.3], and 19 subjects (19/32,67.9%) met the minimally important difference. Statistically significant improvements were also noted in fecal incontinence frequency, quality of life, and overactive bladder symptom bother and quality of life (all p < 0.01).. Darifenacin can be considered a highly effective early intervention in women suffering from double incontinence.. Bladder Antimuscarinic Medication and Accidental Bowel Leakage (BAMA), https://clinicaltrials.gov/ct2/show/NCT03543566 , NCT03543566.

Topics: Aged; Benzofurans; Cohort Studies; Fecal Incontinence; Female; Humans; Middle Aged; Prospective Studies; Pyrrolidines; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urinary Incontinence, Urge

Topics: Benzofurans; Fecal Incontinence; Female; Humans; Pyrrolidines; Urinary Incontinence