Scolapio, James S.

Background —Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT 3 ) antagonist restores postprandial colonic tone towards normal in carcinoid patients. Aims —To evaluate the medium term 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 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 5HT 3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.

Objective: To summarize the pharmacology, development, and clinical application of teduglutide (ALX-0600), a glucagon-like peptide-2 (GLP-2) analog for the treatment of short bowel syndrome (SBS). Data Sources: Clinical literature, including both primary sources and review articles, was accessed through a search of the MEDLINE databases (1980–March 2006). Key search terms included teduglutide, ALX-0600, glucagon-like peptide-2, short bowel syndrome, short gut, and intestinal adaptation. Clinical trial and drug data were supplied by the manufacturer, NPS Pharmaceuticals. Study Selection and Data Extraction: Review articles, abstracts, and clinical studies related to GLP-2 and its analog, teduglutide, were analyzed. An evaluation of the research exploring teduglutide for the management of SBS was conducted. Relevant information was then selected. Data Synthesis: Research has revealed that administration of GLP-2 to patients following major small bowel resection improves intestinal adaptation and nutrient absorption. Teduglutide is an enzyme-resistant GLP-2 analog that shows promise in preventing intestinal injury, restoring mucosal integrity, and enhancing intestinal absorptive function. Conclusions: Data from ongoing clinical trials indicate that teduglutide may have the ability to enhance intestinal absorptive capacity in patients with SBS. Further studies and the completion of Phase III trials are necessary to determine the appropriate dosage and length of treatment for patients with SBS to gain optimal therapeutic benefit from this drug.