title: Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo-controlled and dose-finding study.
abstract: BACKGROUND
  Lubiprostone is a prostone analog with a novel mechanism of action involving type-2 chloride channel activation. The aim of this work was to perform a dose-finding study for lubiprostone for the treatment of constipation with or without irritable bowel syndrome (IBS) in Japan.
  
  
  METHODS
  A total of 170 patients (128 without IBS and 42 with IBS) with chronic idiopathic constipation (CIC) randomly received a placebo (n=42) or 16μg (n=41), 32μg (n=43), or 48μg (n=44) of lubiprostone daily for 2weeks.
  
  
  RESULTS
  There was a statistically significant and dose-dependent increase in change from baseline in the weekly average number of spontaneous bowel movements at week 1 (placebo: 1.5±0.4; 16μg: 2.3±0.4, 32μg: 3.5±0.5; and 48μg: 6.8±1.1, per week, mean±SE; P<0.0001). These primary endpoint results were significant on stratified analysis when patients were limited to those without IBS (P<0.0001). The primary endpoint in patients with IBS treated with 48μg of lubiprostone was significantly better than those given placebo (P=0.0086). Dose dependency was also seen for the secondary efficacy endpoints. Lubiprostone produced no serious side effects.
  
  
  CONCLUSIONS
  Our results suggest that lubiprostone produced a steady and effective improvement in the symptoms of CIC with or without IBS in a dose-dependent manner with a good safety profile and tolerability in a Japanese population.
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. sfukudo@med.tohoku.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Fukudo
authors.forename: M
authors.initials: M
authors.lastname: Hongo
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: R
authors.initials: R
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D044466:Asian People; D018118:Chloride Channels / Q000378:metabolism; D003248:Constipation / Q000188:drug therapy*; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D000068238:Lubiprostone; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome
chemical_list: D018118:Chloride Channels; D010919:Placebos; D000068238:Lubiprostone; D000527:Alprostadil