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Review article: clinical pharmacology of alosetron.

Author(s): Gunput MD

Affiliation(s): Glaxo Wellcome Research and Development, Greenford, Middlesex, UK. mdg26058@glaxowellcome.co.uk

Publication date & source: 1999-05, Aliment Pharmacol Ther., 13 Suppl 2:70-6.

Publication type: Review

Alosetron, a new 5-HT3 antagonist is in development for the treatment of the irritable bowel syndrome. A series of randomized placebo-controlled double-blind clinical pharmacology studies have been performed in healthy volunteers and irritable bowel syndrome patients to evaluate the pharmacokinetics and some of the pharmacodynamic properties of this drug. Alosetron was shown to dose-dependently inhibit the 5-HT-induced skin flare response, increase colonic transit time and increase basal jejunal water and electrolyte absorption, in healthy volunteers. In irritable bowel syndrome patients, alosetron increased colonic compliance. Alosetron had no effect on the perception of gastric distension or on meal-stimulated gastric acid secretion. Orally alosetron has approximately 60% bioavailability and a half-life of 1.5 h. At doses of 1 mg or more, it has a pharmacodynamic duration of action which justifies twice a day dosing. These data support the potential use of alosetron in the treatment of irritable bowel syndrome.

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