Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging.
BACKGROUND
5-HT(3) antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility.


OBJECTIVE
To assess the effects of ondansetron compared with placebo in healthy volunteers on SBWC and motility in two different groups of subjects, one studied using MRI and another using manometry.


METHODS
Healthy volunteers were given either a placebo or ondansetron on the day prior to and on the study day. Sixteen volunteers underwent baseline fasting and postprandial MRI scans for 270 min. In a second study, a separate group of n = 18 volunteers were intubated and overnight migrating motor complex (MMC) recorded. Baseline MRI scans were carried out after the tube was removed.


RESULTS
Fasting SBWC was markedly increased by ondansetron (P < 0.0007). Ondansetron reduced the overall antroduodenal Motility Index (P < 0.04). The subjects who were intubated had significantly lower fasting SBWC (P < 0.0002) compared with the group of subjects who were not intubated.


CONCLUSIONS
The 5-HT(3) receptor antagonism increased fasting small bowel water. This was associated with reduced fasting antroduodenal Motility Index which may explain the clinical benefit of such drugs.
Marciani
L
L
Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, UK.
Wright
J
J
Foley
S
S
Hoad
C L
CL
Totman
J J
JJ
Bush
D
D
Hartley
C
C
Armstrong
A
A
Manby
P
P
Blackshaw
E
E
Perkins
A C
AC
Gowland
P A
PA
Spiller
R C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D003967:Diarrhea / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008365:Manometry; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use*; D019518:Postprandial Period; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D012702:Serotonin Antagonists; D017294:Ondansetron