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Lubiprostone: Chloride channel activator for chronic constipation
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Journal Article
Lubiprostone: Chloride channel activator for chronic constipation
2006
Overview
Chronic constipation is a common and costly health problem occurring in ∼4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms.
The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation.
Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966–July 10, 2006). Search terms utilized were
lubiprostone, RU-0211, and
chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included.
Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 μg of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (
P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food.
Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.
Publisher
EM Inc USA,Excerpta Medica,Elsevier Limited
Subject
/ Alprostadil - analogs & derivatives
/ Alprostadil - pharmacokinetics
/ Alprostadil - therapeutic use
/ Animals
/ Biological and medical sciences
/ Chloride Channels - metabolism
/ Colon
/ Fatty Acids - adverse effects
/ Fatty Acids - pharmacokinetics
/ Fatty Acids - therapeutic use
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Humans
/ Ion Channel Gating - drug effects
/ lubiprostone, RU-0211, chronic constipation, review
/ Pharmacology. Drug treatments
/ Rectum
