Gut 1999;44:682-686 ( May )
Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans
E P Bouras, M Camilleri, D D Burton, S McKinzie
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
Correspondence to: Dr M Camilleri, Mayo Clinic, GI UnitAlfred 2-435, 200 First St SW, Rochester, MN 55905, USA.
Accepted for publication 6 January 1999
BACKGROUNDPrucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro.
AIMSTo evaluate the effects of prucalopride on gastrointestinal and colonic transit.
METHODSA 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.
RESULTSThere 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.
CONCLUSIONPrucalopride 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
© 1999 by Gut