Reviews for Primary Care - Fall 2007 - (Page 22) Chronic Constipation and Functional Bowel Disorders continued Intent-to-Treat Population 7 Mean spontaneous bowel movement frequency 6 5 4 3 2 1 0 Baseline † † † † Lubiprostone 24 g bid Placebo Week 1 Week 2 Week 3 Week 4 N 237 *Age of subjects was not specified. † All points from weeks 1–4 were statistically significant. Figure 8. Impact of lubiprostone on number of spontaneous bowel movements.* Adapted from Johanson JF et al.56 Chloride Channel Activators in Patients With Chronic Constipation or IBS-C Camilleri and colleagues performed a 2-week, randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 g twice daily) on small bowel and colon transit in 30 healthy volunteers over 24 and 48 hours.55 Using validated methods that measured gastrointestinal and colonic transit, gastric volume, maximum tolerated volume, and postprandial symptoms, lubiprostone was found to significantly accelerate small bowel (P .017) and colonic transit (P .033) at 24 hours. Lubiprostone is currently the only fully available prescription medication indicated for the treatment of chronic idiopathic constipation in the adult population.25 Clinical trials indicate that lubiprostone can quickly induce a spontaneous bowel movement, with 61% of patients reporting a spontaneous bowel movement within 24 hours of receiving their first dose of lubiprostone.56 There have been 2 phase III pivotal trials evaluating the treatment effects of lubiprostone in patients with chronic constipation. In one of these, 242 patients with chronic constipation were enrolled in a 4-week, randomized, placebo-controlled trial to assess changes in the frequency of spontaneous bowel movements. Patients who received lubiprostone 24 g twice daily experienced significantly more spontaneous bowel movements than patients who received placebo (P .002 at all weeks).57 Similar results were observed in the second phase III trial involving 237 subjects with chronic constipation (Figure 8).56 In this trial, significantly more patients (61%) given lubiprostone 24 g twice daily (n 119) were able to have a spontaneous bowel movement within 24 hours of the initial dose compared with 31% given placebo (n 118) (P .0001). These differences persisted throughout the 4 weeks of the trial. In a 48-week, open-label safety study, Ueno and colleagues demonstrated that lubiprostone provided sustained improvement in constipation severity, abdominal bloating, and abdominal discomfort.58 Additionally, long-term use of lubiprostone over this period of time did not induce tachyphylaxis, nor did discontinuation result in a rebound worsening of constipation. The most common adverse events observed by patients taking lubiprostone Figure 9. Impact of lubiprostone* on symptoms in adults with IBS-C. Adapted from Drossman DA et al.61 25 P 20 Patients achieving overall response (%) 17.9 .001 15 10.1 10 5 0 Lubiprostone 8 g bid (n 780) Control (n 387) *Lubiprostone is indicated for chronic idiopathic constipation and is not indicated for the treatment of IBS-C. 22 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE
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