Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.
Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.
Camilleri
Michael
M
Clinical Enteric Neuroscience Translational and Epidemiological Research Group, Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
Bharucha
Adil E
AE
Ueno
Ryuji
R
Burton
Duane
D
Thomforde
George M
GM
Baxter
Kari
K
McKinzie
Sanna
S
Zinsmeister
Alan R
AR
D000293:Adolescent; D000328:Adult; D000527:Alprostadil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology; D004311:Double-Blind Method; D005227:Fatty Acids / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D000068238:Lubiprostone; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013270:Stomach / Q000502:physiology*
D018118:Chloride Channels; D005227:Fatty Acids; D010919:Placebos; D000068238:Lubiprostone; D000527:Alprostadil