Prucalopride: novel drug for chronic idiopathic constipation
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20193204Keywords:
Chronic Idiopathic Constipation, 5 HT4 receptor agonists, Prokinetic agents, PrucaloprideAbstract
Chronic Idiopathic Constipation (CIC), defined as constipation in which the underlying cause is unknown, is a common medical illness with a profound negative impact on health-related quality of life and increased propensity for life threatening complications. Current treatment for CIC includes lifestyle modifications, over-the-counter medications, and prescription medications. Presently, the only approved, prescription products for CIC in the US are prosecretory agents. However, the current knowledge that serotonin plays an important role in colonic motility has opened new horizons in the treatment of CIC promoting use of prokinetic agents with a different mechanism of action. Prucalopride is a highly selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist that enhances propulsive motor patterns in the large intestine due to a high affinity for 5-HT4 receptors in gastrointestinal (GI) tissues. The onset of action of Prucalopride is fast, shows rapid absorption, oral bioavailability of 93% and linear pharmacokinetics. Most common adverse reactions seen are headache, nausea, diarrhea, and abdominal pain. Clinical trials for Prucalopride have been positive, and results suggest that the drug may be a new safe and effective option for CIC treatment, especially for patient’s refractory to prosecretory agents. As a prescription drug for the management of constipation and given the virtual demise of other prokinetic agents for this indication, prucalopride competes primarily with another class of agents: those that stimulate secretion. With Shire Pharmaceuticals having already received US FDA approval in Dec 2018, Prucalopride may soon be a new addition to the mounting armoury of drugs against CIC.
Metrics
References
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterol. 2006Apr1;130(5):1480-91.
Belsey J, Greenfield S, Candy D, Geraint M. Systematic review: impact of constipation on quality of life in adults and children. Alimentary pharmacol & therapeutics. 2010May;31(9):938-49.
Wald A, Scarpignato C, Kamm MA, Mueller‐Lissner S, Helfrich I, Schuijt C, et al. The burden of constipation on quality of life: results of a multinational survey. Alimentary pharmacol & therapeutics. 2007Jul1;26(2):227-36.
Cook IJ, Talley NJ, Benninga MA, Rao SS, Scott SM. Chronic constipation: overview and challenges. Neurogastroenterol and Motility. 2009Dec;21:1-8.
Camilleri M, Ford AC, Mawe GM, Dinning PG, Rao SS, Chey WD, et al. Chronic constipation. Nature reviews Disease primers. 2017Dec14;3:17095.
Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. The American J Gastroenterol. 2011Sep;106(9):1582.
Bosshard W, Dreher R, Schnegg JF, Büla CJ. The treatment of chronic constipation in elderly people. Drugs Aging. 2004Dec1;21(14):911-30.
Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004Apr;99(4):750.
Peppas G, Alexiou VG, Mourtzoukou E, Falagas ME. Epidemiology of constipation in Europe and Oceania: a systematic review. BMC gastroenterol. 2008 Dec;8(1):5.
Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde G. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterol. 2000Mar 1;118(3):463-8.
Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J et al. Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study. J cardiovascular pharmacol and therape. 2010Jun;15(2):151-7.
Tack J, Van Outryve M, Beyens G, Kerstens R, Vandeplassche L. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009Mar1;58(3):357-65.
Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014,39:239-53.
Mawe GM, Hoffman JM. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013,10:473-86.
Bassotti G, Chistolini F, Nzepa FS, Morelli A. Colonic propulsive impairment in intractable slow-transit constipation. Arch Surg. 2003,138:1302-4.
De Schryver AM, Andriesse GI, Samsom M, Smout AJ, Gooszen HG, Akkermans LM. The effects of the specific 5HT(4) receptor agonist, prucalopride, on colonic motility in healthy volunteers. Aliment Pharmacol Ther. 2002,16:603-12.
De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil. 2008,20:99-112.
Van De Velde VJ, Ausma JJ, Vandeplassche LM. Kinetics and absolute oral bioavailability of prucalopride. Gastroenterol. 2010,138(5 Suppl 1):S-230.
Tack J, Quigley E, Camilleri M, Vandeplassche L, Kerstens R. Efficacy and safety of oral prucalopride in women with chronic constipation in whom laxatives have failed: an integrated analysis. United European Gastroenterol J. 2013,1:48-59.
Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterol. 2001Feb1;120(2):354-60.
De Schryver AM, Andriesse GI, Samsom M, Smout AJ, Gooszen HG, Akkermans LM. The effects of the specific 5HT4 receptor agonist, prucalopride, on colonic motility in healthy volunteers. Alimentary pharmacol Ther. 2002Mar1;16(3):603-12.
Emmanuel A, Cools M, Vandeplassche L, Kerstens R. Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis. The American J gastroenterol. 2014Jun;109(6):887.
Diederen K, Mugie SM, Benninga MA. Efficacy and safety of prucalopride in adults and children with chronic constipation. Expert Opin. Pharmacother. 2015,16:407-416.
Stillman MJ, Tepper DE, Tepper SJ, Cho L. QT prolongation, Torsade de Pointes, myocardial ischemia from coronary vasospasm, and headache medications. Part 2:review of headache medications, drug-drug interactions, QTc prolongation, and other arrhythmias. Headache. 2013,53:217-24.
Mendzelevski B, Ausma J, Chanter DO, Robinson P, Kerstens R, Vandeplassche L, et al. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study. Br J Clin Pharmacol. 2012,73:203-9.
Conlon K, De Maeyer JH, Bruce C, Schuurkes JA, Christie L, McRedmond J, et al. Nonclinical Cardiovascular Studies of Prucalopride, a Highly Selective 5-Hydroxytryptamine 4 Receptor Agonist. J Pharmacol Exper Ther. 2018 Feb1;364(2):156-69.
Gilsenan A, Fortuny J, Plana E, Ruigómez A, Karlsson P, Flynn RW, et al. 386-Non-interventional cohort study of the relative incidence of major cardiovascular events among patients initiating prucalopride versus a matched comparator cohort initiating polyethylene glycol 3350 (PEG). Gastroenterol. 2018May 1;154(6):S-92.
Leelakusolvong S, Ke M, Zou D, Choi SC, Tack J, Quigley EM, et al. Factors predictive of treatment-emergent adverse events of prucalopride: an integrated analysis of four randomized, double-blind, placebo-controlled trials. Gut Liver. 2015,9:208-13.
Camilleri M, Beyens G, Kerstens R, Robinson P, Vandeplassche L. Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study. Neurogastroenterol Motil. 2009,21:1256-e117
Sanger GJ, Quigley EM. Constipation, IBS and the 5-HT4 receptor: what role for prucalopride? Clinical Medicine. Gastroenterol. 2010Jan;3:CGast-S4136.
Bouras EP, Camilleri M, Burton DD, McKinzie S. Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut. 1999May1;44(5):682-6.
Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterol. 2001Feb1;120(2):354-60.
Coremans G. Prucalopride: the evidence for its use in the treatment of chronic constipation. Core evidence. 2008Jun;3(1):45.
De Schryver AM, Andriesse GI, Samsom M, Smout AJ, Gooszen HG, Akkermans LM. The effects of the specific 5HT4 receptor agonist, prucalopride, on colonic motility in healthy volunteers. Alimentary Pharmacol Ther. 2002Mar1;16(3):603-12.
Quigley EM. Prucalopride: safety, efficacy and potential applications. Therapeutic advances in gastroenterol. 2012 Jan;5(1):23-30.
Camilleri M., Piessevaux H., Yiannakou Y., Tack J., Kerstens R., Quigley E, et al. Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials. Dig Dis Sci. 2016;61:2357-72.
Downloads
Published
How to Cite
Issue
Section
