Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers.
BACKGROUND
Alosetron is a potent and selective 5-HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non-constipated irritable bowel syndrome.


OBJECTIVE
To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2).


METHODS
Thirteen patients with irritable bowel syndrome and 12 healthy volunteers.


METHODS
Both studies were randomized, double-blind, placebo-controlled with a two-way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio-opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X-ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time.


RESULTS
Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047).


CONCLUSIONS
Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non-constipated irritable bowel syndrome.
Houghton
L A
LA
Department of Medicine, University Hospital of South Manchester, Manchester, UK. lahoughton@man.ac.uk
Foster
J M
JM
Whorwell
P J
PJ
D000328:Adult; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003109:Colonic Diseases, Functional / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron