Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea.
BACKGROUND
Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients.


OBJECTIVE
To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea.


METHODS
In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication.


RESULTS
There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit.


CONCLUSIONS
Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.
Saslow
S B
SB
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
Scolapio
J S
JS
Camilleri
M
M
Forstrom
L A
LA
Thomforde
G M
GM
Burton
D D
DD
Rubin
J
J
Pitot
H C
HC
Zinsmeister
A R
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002243:Carbolines / Q000008:administration & dosage* / Q000627:therapeutic use; D002276:Carcinoid Tumor / Q000150:complications / Q000503:physiopathology / Q000556:secondary*; D003106:Colon / Q000503:physiopathology; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D007414:Intestinal Neoplasms / Q000150:complications / Q000503:physiopathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron