Effect of a chloride channel activator, lubiprostone, on colonic sensory and
motor functions in healthy subjects.
Author(s): Sweetser S, Busciglio IA, Camilleri M, Bharucha AE, Szarka LA, Papathanasopoulos
A, Burton DD, Eckert DJ, Zinsmeister AR.
Affiliation(s): Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER)
Group, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Publication date & source: 2009, Am J Physiol Gastrointest Liver Physiol. , 296(2):G295-301
Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in
treatment of chronic constipation and constipation-predominant irritable bowel
syndrome. The study aim was to compare effects of lubiprostone and placebo on
colonic sensory and motor functions in humans. In double-blind, randomized
fashion, 60 healthy adults received three oral doses of placebo or 24 microg
lubiprostone per day in a parallel-group, placebo-controlled trial. A
barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy
and fluoroscopy. We measured treatment effects on colonic sensation and motility
with validated methods, with the following end points: colonic compliance,
fasting and postprandial tone and motility indexes, pain thresholds, and sensory
ratings to distensions. Among participants receiving lubiprostone or placebo, 26
of 30 and 28 of 30, respectively, completed the study. There were no overall
effects of lubiprostone on compliance, fasting tone, motility indexes, or
sensation. However, there was a treatment-by-sex interaction effect for
compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in
women (P = 0.06) and an overall decreased colonic tone contraction after a
standard meal relative to fasting tone (P = 0.014), with greater effect in women
(P < 0.01). Numerical differences of first sensation and pain thresholds (P =
0.11 in women) in the two groups were not significant. We concluded that oral
lubiprostone 24 microg does not increase colonic motor function. The findings of
decreased colonic compliance and decreased postprandial colonic tone in women
suggest that motor effects are unlikely to cause accelerated colonic transit with
lubiprostone, although they may facilitate laxation. Effects of lubiprostone on
sensitivity deserve further study.
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