Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist.
BACKGROUND
No currently available treatment provides consistent relief of irritable bowel syndrome. Colonic sensory and motor function are modulated partly through 5HT3-receptors.


OBJECTIVE
To evaluate effects of the 5HT3-receptor antagonist, alosetron, in irritable bowel syndrome.


METHODS
Randomized, double-blind, placebo-controlled, dose-ranging (1, 2, 4, 8 mg b.d. alosetron), 12-week trial in 370 patients with diarrhoea-predominant or alternating constipation and diarrhoea irritable bowel syndrome. Weekly measurement of adequate relief was the key end-point; other irritable bowel syndrome symptoms were collected daily using an electronic phone system.


RESULTS
Alosetron (1 mg or 2 mg b.d.) significantly (P < 0.05 vs. placebo) increased the proportion of females, but not males, reporting adequate relief. Stool consistency, frequency and percentage days with urgency improved over placebo (P < 0.05) within the first month with all doses of alosetron, and persisted throughout the trial with all doses in female patients. With 1 mg b.d. alosetron, females had improved stool consistency and urgency within the first week, and adequate relief and improved stool frequency within the first 2 weeks. There was no consistent improvement in bowel function among male patients.


CONCLUSIONS
In female irritable bowel syndrome patients with predominant diarrhoea or alternating constipation and diarrhoea, alosetron is effective in treatment of abdominal pain and discomfort and bowel-related symptoms.
Camilleri
M
M
Gastroenterology Research Unit, Mayo Foundation, Rochester, Minnesota 55905, USA. camilleri.michael@mayol.edu
Mayer
E A
EA
Drossman
D A
DA
Heath
A
A
Dukes
G E
GE
McSorley
D
D
Kong
S
S
Mangel
A W
AW
Northcutt
A R
AR
D015746:Abdominal Pain / Q000188:drug therapy; D000328:Adult; D002170:Canada; D002243:Carbolines / Q000008:administration & dosage*; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D003967:Diarrhea / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D012737:Sex Factors; D016896:Treatment Outcome; D006113:United Kingdom; D014481:United States
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron