Journal Mobile Options
Table of Contents
Vol. 67, No. 1-2, 2003
Issue release date: 2003

Prucalopride Is Effective in Patients with Severe Chronic Constipation in Whom Laxatives Fail to Provide Adequate Relief

Results of a Double-Blind, Placebo-Controlled Clinical Trial

Coremans G. · Kerstens R. · de Pauw M. · Stevens M.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin4 receptor agonist with enterokinetic properties. Aims: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre. Methods: After 4-weeks’ run in, patients were randomized to 4 weeks’ once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks’ treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study). Results: Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters. Conclusions: Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Sonnenberg A, Koch TR: Epidemiology of constipation in the United States. Dis Colon Rect 1989a;32:1–8.
  2. Johanson JF, Sonnenberg A, Koch TR: Clinical epidemiology of chronic constipation. J Clin Gastroenterol 1989;11:525–536.
  3. Stewart WF, Liberman JN, Sandler RS, et al: Epidemiology of constipation (EPOC) in the United States: Relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999;94:3530–3540.
  4. Drossman DA, Sandler RS, McKee DC, et al: Bowel patterns among subjects not seeking health care: Use of a questionnaire to identify a population with bowel dysfunction. Gastroenterology 1982;83:529–534.
  5. Everhart JE, Go VLW, Johannes RS, et al: A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989;34:1134–1162.
  6. Sonnenberg A, Koch TR: Physician visits in the United States for constipation: In 1958 to 1986. Dig Dis Sci 1989b;34:601–611.
  7. Thompson WG, Heaton KW: Functional bowel disorders in apparently healthy people. Gastroenterology 1980;79:283–288.
  8. Thompson WG, Creed F, Drossman DA, et al: Functional bowel disorders and chronic functional abdominal pain. Gastroenterol Int 1992;5:75–91.
  9. Thompson WG, Longstreth GF, Drossman DA, et al: Functional bowel disorders and functional abdominal pain. Gut 1999;45(suppl II):II43–47.
  10. Glia A, Lindberg G: Quality of life in patients with different types of functional constipation. Scand J Gastroenterol 1997;32:1083–1089.
  11. Gattuso JM, Kamm M: Review article: The management of constipation in adults. Aliment Pharmacol Ther 1993;7:847–850.
  12. Ashraf W, Park F, Lof J, et al: Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation. Aliment Pharmacol Ther 1995;9:639–647.
  13. Badiali D, Corazzini E, Habib FI, et al: Effect of wheat bran in treatment of chronic nonorganic constipation: A double blind controlled trial. Dig Dis Sci 1995;40:349–356.
  14. Odes HS, Madar Z: A double blind trial of a celandin, aloevera and psyllium laxative preparation in adult patients with constipation. Digestion 1991;49:65–71.
  15. Jones M, Dubois D, Talley N: Laxatives in chronic constipation: A statistical meta-analysis [abstract]. Gastroenterology 1999;116:A67.
  16. Briejer MR, Schuurkes JAJ, Sarna SK: Idiopathic constipation: Too few stools and too little knowledge. Trends Pharmacol Sci 1999;20:1–3.
  17. Basotti G, Gaburri M, Imbimbo B, et al: Colonic mass movements in idiopathic chronic constipation. Gut 1988;29:1173–1179.
  18. Emmanuel AV, Kamm MA, Roy AJ, et al: Effect of a novel prokinetic drug, RO93877, on gastrointestinal transit in healthy volunteers. Gut 1998;42:511–516.
  19. Jin J-G, Foxx-Orenstein AE, Grider JR: Propulsion in guinea pig colon induced by 5-hydroxytriptamine (HT) via 5-HT4 and 5-HT3 receptors. J Pharmacol Exp Ther 1999;288:93–97.
  20. Grider JR, Foxx-Orenstein AE, Jin J-G: 5-Hydroxytryptamine-4 receptor agonists initiate the peristaltic reflex in human, rat and guinea pig intestine. Gastroenterology 1998;115:370–380.
  21. Briejer MR, Meulemans AL, Van Daele P, et al: R093877 induces giant migrating contractions (GMC) and alters colonic motility patterns in awake dogs (abstract). Neurogastroenterol Motil 1998;10:62.
  22. Briejer M, Meulemans A, Bosmans J-P, et al: In vitro pharmacology of the novel enterokinetic R093877 (abstract). Gastroenterology 1997;112:A705.
  23. Mannaert E, Van Bortel L, Woestenborghs R, et al: Single-dose and once-daily pharmacokinetics and effects of food on prucalopride in humans (abstract). Gut 1999;45(suppl V):P0252.
  24. Bouras EP, Camilleri M, Burton DD, et al: Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut 1999;44:682–686.
  25. Cummings JH, Wiggins HS: Transit through the gut measured by analysis of a single stool. Gut 1976;17:219–223.
  26. Ghoos Y, Vantrappen G: Clean collection and manipulation of stools. Lancet 1977;i:884–885.
  27. Preston DM, Lennard-Jones JE: Severe chronic constipation of young women: ‘Idiopathic slow transit constipation’. Gut 1986;27:41–48.
  28. Cleveland MvB, Flavin DP, Ruben RA, Epstein RM, Clark GE: New polyethylene glycol laxative for treatment of constipation in adults. South Med J 2001;94:478–481.
  29. Hagger R, Benson M, Lloyd R, et al: A placebo-controlled study to evaluate the effect on colonic transit of R093877 in healthy volunteers (abstract). Gastroenterology 1998;114:A759.
  30. Otten MH, Schneider H, Wurzer H, et al: A double-blind, placebo-controlled evaluation of safety and efficacy of 12-week, twice daily treatment with prucalopride in patients with chronic constipation (abstract). Gastroenterology 1999;116:A1055.
  31. Van ‘t Klooster G, De Pauw M, Crabbé R: Tolerability, pharmacokinetics and pharmacodynamics of prucalopride in healthy volunteers (abstract). Gut 1999;45(suppl V):P0264.
  32. Poen AC, Felt-Bersma RJF, Meuwissen SGM: A placebo-controlled study to evaluate the effects of repeated oral doses of R093877 on gastrointestinal transit and anorectal manometry in healthy volunteers (abstract). Gastroenterology 1997;112:A807.
  33. Vandeplassche G, Crabbé R, De Smedt H, et al: A placebo-controlled study to evaluate the effects of single increasing oral doses of R093877 (R) on bowel habit, safety and tolerability in healthy volunteers (abstract). Gastroenterology 1997;112:A843.
  34. Felt-Bersma RJF, Bouchoucha M, Wurzer H, et al: Effects of a new enterokinetic drug, prucalopride, on symptoms of patients with chronic constipation: A double-blind, placebo-controlled, multicenter study in Europe (abstract). Gastroenterology 1999;116:A992.
  35. Miner PB Jr, Nichols T, Silvers DR, et al: The efficacy and safety of prucalopride in patients with chronic constipation (abstract). Gastroenterology 1999;116:A1043.
  36. Nagakura Y, Akuzawa S, Miyata K, Kamato T, Suzuki T, Ito H, Yamaguchi T: Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor. Pharmacol Res 1999;39:375–382.
  37. Kajuta S, Ito C, Kawamura R, Yasuda S, Isobe Y, Fukushima K: Pharmacological characterization of a novel 5-HT4 receptor agonist, TS-951, in vitro. Pharmacology 2001;63:8–16.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50