Lubiprostone: in constipation-predominant irritable bowel syndrome.
Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.
Carter
Natalie J
NJ
Wolters Kluwer Health, Adis, Auckland, New Zealand. demail@adis.co.nz
Scott
Lesley J
LJ
D000527:Alprostadil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D003248:Constipation / Q000150:complications* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000188:drug therapy*; D000068238:Lubiprostone; D016032:Randomized Controlled Trials as Topic
D000068238:Lubiprostone; D000527:Alprostadil