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


OBJECTIVE
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 48 hours.


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.


CONCLUSIONS
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.
Bouras
E P
EP
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Camilleri
M
M
Burton
D D
DD
McKinzie
S
S
D000293:Adolescent; D000328:Adult; D001572:Benzofurans / Q000009:adverse effects / Q000494:pharmacology*; D003106:Colon / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007421:Intestine, Small / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*
D001572:Benzofurans; D005765:Gastrointestinal Agents; D017366:Serotonin Receptor Agonists; C406662:prucalopride