Effects of trimebutine on colonic function in patients with chronic idiopathic constipation: evidence for the need of a physiologic rather than clinical selection.
A double-blind crossover study on the effects of trimebutine on large bowel function was performed in 24 consecutive patients complaining of chronic idiopathic constipation. Their stool frequency, colonic transit time, and colonic electrical activity were measured. They were divided into a group of constipated patients with "normal" transit time (less than 40 hours) (n = 12) and another group of constipated patients with "delayed" transit time (more than 40 hours) (n = 12). The patients received trimebutine (200 mg/day per os) for one month and a placebo for another month, at random, with a washout period in between. Results show that stool frequency increased (P < 0.001) in all patients as soon as they entered the study; there was no difference between trimebutine and placebo. Colonic transit time was significantly reduced (P < 0.05) with trimebutine in patients with delayed transit time (from 105 +/- 19 hours to 60 +/- 11 hours; mean +/- SE), while it did not change with placebo (from 103 +/- 17 hours to 95 +/- 10 hours). It was slightly but not significantly increased in patients with normal transit time following trimebutine therapy. Electrical activity was not influenced by trimebutine or placebo in constipated patients with normal transit time, either before or after a meal. The number of propagating bursts during the postprandial period was significantly (P < 0.05) increased in patients with delayed transit (from 2.1 +/- 0.3 bursts/hour to 3.5 +/- 0.6 bursts/hour after trimebutine); it was decreased but not significantly with placebo (from 2.6 +/- 0.8 bursts/hour to 1.6 +/- 0.6 bursts/hour) in the same group of patients. Thus, stool frequency in patients with chronic idiopathic constipation was influenced mainly by a placebo effect. Colonic transit time was reduced by trimebutine, but this was found only in patients with delayed colonic transit; myoelectric propagating bursts were increased, and this probably explains the improvement. In conclusion, trimebutine may be of value in the treatment of patients with chronic idiopathic constipation, provided that a careful pathophysiologic evaluation reveals that they have a colonic transit time that exceeds the normal range. In addition, this study provides some argument for selecting patients with functional motor disorders of the large intestine to be entered into a research protocol or to be treated not on the basis of what they complain about--the symptom--but on the basis of some kind of measurement of dysfunction--a corresponding sign.
Schang
J C
JC
Department of Surgery, Faculté de Médecine, Université de Sherbrooke, Québec, Canada.
Devroede
G
G
Pilote
M
M
D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003248:Constipation / Q000209:etiology / Q000503:physiopathology*; D003672:Defecation; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014287:Trimebutine / Q000494:pharmacology*
D014287:Trimebutine