Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety.

Article Details

Citation

Johanson JF, Ueno R

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety.

Aliment Pharmacol Ther. 2007 Jun 1;25(11):1351-61.

PubMed ID
17509103 [ View in PubMed
]
Abstract

BACKGROUND: Lubiprostone, a locally acting type-2 chloride channel activator, induces intestinal fluid secretion. AIM: To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation. METHODS: A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked. RESULTS: Over the double-blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1-6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P < or = 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P < or = 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P < or = 0.009). The most common AEs were nausea, headache and diarrhoea. CONCLUSIONS: Lubiprostone improved SBM rates in a dose-dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to-benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
LubiprostoneChloride channel protein 2ProteinHumans
Yes
Inducer
Details