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. 1999 May;44(5):682–686. doi: 10.1136/gut.44.5.682

Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans

E Bouras 1, M Camilleri 1, D Burton 1, S McKinzie 1
PMCID: PMC1727485  PMID: 10205205

Abstract

BACKGROUND—Prucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. 
AIMS—To evaluate the effects of prucalopride on gastrointestinal and colonic transit. 
METHODS—A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0.5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48hours. 
RESULTS—There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0.12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. 
CONCLUSION—Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation. 



Keywords: benzofuran; prucalopride; motility; transit; colon; gastrointestinal

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Figure 1 .

Figure 1

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Experimental procedure. 


Figure 2 .

Figure 2

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Effect of prucalopride on overall colonic transit (geometric centre) at 4 (A), 8 (B), 24 (C), and 48 (D) hours. ANOVA shows significant overall drug effect (at least one dose at each time point; *p<0.05) at all times. Dunnett's test shows significant effects of the 0.5 and 2.0 mg doses versus placebo. 


Figure 3 .

Figure 3

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Effect of prucalopride on proximal colonic emptying half time; the drug has an overall significant effect on t1/2; the t1/2 values observed with the 0.5 and 2.0 mg doses are significantly lower than those with placebo (Dunnett's test, *p<0.05). 


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