Lubiprostone for the Treatment of Functional Constipation in Children

Objectives:Pediatric functional constipation is common; effective, easily administered treatment options are limited. Lubiprostone is an oral chloride channel protein-2 activator that stimulates gastrointestinal fluid secretion, softens stools, and facilitates bowel movements (BMs). We evaluated the safety and effectiveness of lubiprostone in children and adolescents with functional constipation.Methods:Patients 12 kg, 17 years or younger, and with <3 spontaneous BMs (SBMs; ie, BMs that did not occur within 24 hours of rescue medication use) per week were enrolled at 22 US general pediatric and pediatric gastroenterology centers (January 2007-October 2008). Patients received 4 weeks of open-label lubiprostone at doses of 12 g once daily (QD), 12 g twice daily (BID), or 24 g BID based on age and weight. The primary endpoint was SBM frequency during week 1 versus baseline.Results:Of 127 enrolled patients, 124 were treated and analyzed (12 g QD, n=27; 12 g BID, n=65; 24 g BID, n=32), and 109 completed the study. The mean age of treated patients was 10.2 years (range 3-17 years); 65 were boys. Mean SBM frequency significantly increased compared with baseline at week 1 (3.1 vs 1.5 SBMs/week, P<0.0001). SBM frequency was improved significantly from baseline overall (P<0.0001) and for individual dose groups (P0.0062) during weeks 2, 3, and 4. Common (5%) adverse events included nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%), and headache (5.6%). Two patients experienced serious adverse events (unrelated abdominal pain; unrelated sickle cell crisis).Conclusions:Lubiprostone was efficacious and well tolerated in children and adolescents with functional constipation.