Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury.
BACKGROUND
Chronic constipation (CC) often occurs after spinal cord injury (SCI). Prucalopride is a novel, highly selective, specific serotonin4 receptor agonist with enterokinetic properties. We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCL.


METHODS
Double-blind, placebo-controlled, pilot, phase 11, dose-escalation study. After 4 weeks' run in, patients received prucalopride 1 mg (n = 8) or placebo (n = 4); 11 new patients were randomized to prucalopride 2 mg (n = 8) or placebo (n = 3) once daily for 4 weeks. Patients recorded bowel function (diary) and assessed constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100 mm). Colonic transit times were determined.


RESULTS
Compared with run in. mean changes in constipation severity (VAS) increased with placebo, but decreased with prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data showed an improvement in average weekly frequency of all bowel movements over 4 weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a significant reduction in median colonic transit time with 2 mg (n = 4; -38.5 h (95% CI -80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain, and two of these discontinued treatment. There were no clinically relevant effects on any of the safety parameters.


CONCLUSIONS
This pilot study indicates that prucalopride can play an important role in the management of patients with CC due to SCI.
Krogh
K
K
Surgical Research Unit, Arhus Amtssygehus, Denmark.
Jensen
M Bach
MB
Gandrup
P
P
Laurberg
S
S
Nilsson
J
J
Kerstens
R
R
De Pauw
M
M
D000293:Adolescent; D000328:Adult; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology; D003672:Defecation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications*
D001572:Benzofurans; D005765:Gastrointestinal Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C406662:prucalopride; D044422:Receptors, Serotonin, 5-HT4