EFFECT OF A NOVEL PROKINETIC DRUG, R093877, ON GASTROINTESTINAL TRANSIT IN HEALTHY-VOLUNTEERS

Citation
Av. Emmanuel et al., EFFECT OF A NOVEL PROKINETIC DRUG, R093877, ON GASTROINTESTINAL TRANSIT IN HEALTHY-VOLUNTEERS, Gut, 42(4), 1998, pp. 511-516
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
GutACNP
ISSN journal
0017-5749
Volume
42
Issue
4
Year of publication
1998
Pages
511 - 516
Database
ISI
SICI code
0017-5749(1998)42:4<511:EOANPD>2.0.ZU;2-G
Abstract
Background-Stronger prokinetic agents which specifically enhance trans it in different parts of the gut are required. R093877 is a novel 5-HT 4 agonist prokinetic compound which is chemically related to cisapride but believed to have greater effect on colonic activity. Aims-To eval uate the effects of R093877 on bowel function, upper and lower gut tra nsit, visceral sensitivity, and sphincter function in healthy voluntee rs in a double blind, placebo controlled, crossover study. Methods-The study consisted of five consecutive one week periods: no drug treatme nt; active drug treatment with either 1 or 2 mg daily or placebo; wash out; active drug or placebo; no treatment. Seventeen male subjects mai ntained a detailed diary of bowel function for the entire study. Oroca ecal transit (breath hydrogen), whole gut transit (radio-opaque marker s), and anorectal function were assessed at the end of each of the two treatment periods. Blood testing was performed to confirm compliance and for safety analysis. Results-One subject withdrew from the study d ue to side effects while on placebo. Eight subjects completed the stud y on 1 mg and a further eight on 2 mg. Blood testing showed non-compli ance in one subject on the 2 mg dose, and he was excluded from analysi s of all diary and physiological data. Treatment increased the number of stools per week (placebo versus 1 mg, 7.8 versus 13.6, p=0.003; pla cebo versus 2 mg, 8.9 versus 11.3, p=0.15) and the percentage of loose or watery stools (24.2% versus 61.5%, p<0.04; 9.9% versus 40.0%, p<0. 02). Stool frequency and consistency reverted to normal immediately af ter treatment. Treatment shortened orocaecal and whole gut transit in all subjects on both doses. Treatment accelerated orocaecal (76 versus 51 minutes, p=0.007; 63 versus 47 minutes, p=0.07) and whole gut (38. 2 versus 27.0 hours, p=0.05; 44.8 versus 24.0 hours, p<0.04) transit, and decreased the number of retained markers ingested 36 hours previou sly (4.8 versus 1.8, p=0.016; 7.0 versus 4.3, p=0.033). Gut sensitivit y to distension and electrical stimulation, and anal manometry, were u nchanged. Transient headache occurred in seven subjects on R093877 and one subject had mild elevation of liver aminotransferases which resol ved on drug cessation. Conclusions-R093877 is well tolerated by health y subjects and has a marked and consistent effect on stool frequency a nd consistency, and upper gut and colonic transit. It does not affect visceral sensitivity or sphincter function. It holds promise for patie nts with large bowel symptoms or slow gut transit.