BACKGROUND:Serotonin and its type-4 (5-hydroxytryptamine4) receptor play a major role in the physiology of the gastrointestinal tract. The effect of intravenous and/or oral tegaserod, a 5-hydroxytryptamine4 receptor partial agonist, on gastric emptying, small bowel transit and colonic transit has not been studied in detail in humans. AIM: To assess the pharmacodynamic effects of repeated oral and intravenous administration of tegaserod on gastric emptying and small intestine and colonic transit. METHODS: A randomized, placebo-controlled, double-blind, three-way, crossover study of 6 mg oral and 0.6 mg intravenous tegaserod in 12 healthy male subjects was performed. Each treatment arm of the study involved 3 days of twice-daily administration and 1 day of daily administration of the study drugs. RESULTS: In comparison with placebo, oral and intravenous tegaserod significantly increased the gastric emptying rate (P < 0.01), accelerated colonic filling (P < 0.01) and shortened colonic transit at 48 h (P < 0.05). Tegaserod shortened the small intestine transit time by 30% after oral and by 37% after intravenous administration. CONCLUSIONS: In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.
RCT Entities:
BACKGROUND: Serotonin and its type-4 (5-hydroxytryptamine4) receptor play a major role in the physiology of the gastrointestinal tract. The effect of intravenous and/or oral tegaserod, a 5-hydroxytryptamine4 receptor partial agonist, on gastric emptying, small bowel transit and colonic transit has not been studied in detail in humans. AIM: To assess the pharmacodynamic effects of repeated oral and intravenous administration of tegaserod on gastric emptying and small intestine and colonic transit. METHODS: A randomized, placebo-controlled, double-blind, three-way, crossover study of 6 mg oral and 0.6 mg intravenous tegaserod in 12 healthy male subjects was performed. Each treatment arm of the study involved 3 days of twice-daily administration and 1 day of daily administration of the study drugs. RESULTS: In comparison with placebo, oral and intravenous tegaserod significantly increased the gastric emptying rate (P < 0.01), accelerated colonic filling (P < 0.01) and shortened colonic transit at 48 h (P < 0.05). Tegaserod shortened the small intestine transit time by 30% after oral and by 37% after intravenous administration. CONCLUSIONS: In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.
Authors: J A M Smith; D T Beattie; D Marquess; J P Shaw; R G Vickery; P P A Humphrey Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2008-04-16 Impact factor: 3.000
Authors: M L Manini; M Camilleri; M Goldberg; S Sweetser; S McKinzie; D Burton; S Wong; M M Kitt; Y-P Li; A R Zinsmeister Journal: Neurogastroenterol Motil Date: 2009-08-18 Impact factor: 3.598