MEDIUM-TERM EFFECTS OF A NEW 5HT(3) ANTAGONIST, ALOSETRON, IN PATIENTS WITH CARCINOID DIARRHEA

Background-Carcinoid diarrhoea is associated with rapid small bowel an d proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT(3),) antagonist restores postprandial colonic ton e towards normal in carcinoid patients. Aims-To evaluate the medium te rm effects of an oral 5HT(3) 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 ga strointestinal transit was measured by scintigraphy in a three dose (0 .1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, fou r week study. Placebo was given during the first week. Loperamide (2 m g capsules) was used as rescue medication. Results-There were numerica l improvements in median diarrhoea score, stool weight, loperamide use , and overall colonic transit at four hours, but no overall significan t 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 proxim al colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT(3), mechanism in this disorder. Doses of alose tron higher than 2.0 mg twice daily will be required for symptomatic b enefit in carcinoid diarrhoea.