Prucalopride: safety, efficacy and potential applications

Abstract

Chronic constipation is a very common functional gastrointestinal disorder which can be associated with significant impairments in quality of life for some people with the condition. Its management has, traditionally, been based on dietary and lifestyle changes and the use of a variety of laxative agents. The evidence base for the efficacy of the latter is, in many cases, slim. Not surprisingly, many patients remain dissatisfied with laxatives thus leading to the development of more pharmacological approaches. Among these approaches is the use of prokinetic agents; while prior molecules have been troubled by lack of selectivity and cardiac side effects, the new agent, prucalopride, appears to be highly selective for the serotonin 5-HT4 receptor and is, therefore, a potent stimulator of gut motility. In three large pivotal randomized controlled trials, prucalopride has been effective in relieving the cardinal symptoms of chronic constipation; these effects have been sustained in open-label follow up for as long as 18 months. The safety profile has been encouraging and, especially so, the absence of arrhythmogenic potential. Studies in men, in constipation-predominant irritable bowel syndrome and in other motor disorders are eagerly awaited.

Effect of Prucalopride in the Treatment of Chronic Constipation in Asian and Non-Asian Women: A Pooled Analysis of 4 Randomized, Placebo-controlled Studies

“…Overall, prucalopride had an acceptable safety and tolerability profile, which is consistent with those observed in a series of studies. 18,[26][27][28][29][30] However, there were some differences observed in these analyses in TEAEs between Asians and non-Asians (Table 5); significantly more non-Asian women complained at least 1 TEAE in both the treatment groups (P ＜ 0.001). This may be due to the differences in genetic factors (different pharmacokinetic profile) or cultural factors (tendency to report adverse events) between Asian and non-Asian patients.…”

The enteric serotonergic system is altered in patients with diverticular disease

“…Prucalopride, a highly selective 5HT-4R agonist, has received special attention as it is a potent stimulator of gut motility8 9 and exerts facilitating actions on gut smooth muscle cells 10. This effect could be proved in large randomised trials in which prucalopride was effective in the treatment of chronic constipation 11. Although the functions of the 5HT-4R receptor have been extensively characterised, its localisation in the human colon still needs to be elucidated.…”

Prokinetics in the Management of Functional Gastrointestinal Disorders

“…In contrast to cisapride and tegaserod, prucalopride (a benzofuran) is a high affinity, highly selective 5-HT 4 agonist that has very low affinity for other 5-HT receptors and for the hERG-K + cardiac channels. [26][27][28] Its high affinity for the 5-HT 4 receptor confers greater efficacy for prucalopride while low affinity for the hERG-K + channel explains why it has not been shown to be arrhythmogenic 29 ; together they confer a major therapeutic advantage for prucalopride over cisapride. As a prokinetic agent prucalopride promotes colonic motility and transit.…”