Researchers in Minnesota, USA undertook a study to evaluate the dose-ranging pharmacodynamic effects of renzapride, a 5-HT4 receptor full agonist/5-HT3 receptor antagonist.
The research team looked at the drug's effect on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome.
In total, the team recruited 48 patients with constipation-predominant irritable bowel syndrome, of which 46 were women.
The researchers recorded baseline symptoms of each participant for 1 week.
The research group randomly selected 12 patients per group to receive 11–14 days of renzapride (1, 2, or 4 mg) or placebo, once daily.
The team then recorded daily bowel habits and weekly satisfactory relief of IBS symptoms.
At the end of treatment, the researchers made further measurements of gastric emptying, small bowel transit, and colon transit using scintigraphy.
|Bowel function and satisfactory relief were not significantly altered by renzapride|
|Clinical Gastroenterology and Hepatology|
The researchers were able to evaluate the relationship between colon transit and bowel function.
The group found that there was a statistically significant linear dose response to renzapride for colon transit and ascending colon emptying t1/2 but not for gastric emptying.
In addition, ascending colon half-time transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0 hours, respectively.
The researchers also found that improved bowel function scores (stool form and ease of passage, but not frequency) were significantly associated with accelerated colon transit.
Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours.
Bowel function and satisfactory relief were not significantly altered by renzapride, although a type II error cannot be excluded.
No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed.
Dr Michael Camilleri concluded, "Renzapride causes clinically significant dose-related acceleration of colon transit, particularly ascending colonic emptying."
"This acceleration of transit is associated with improvement of bowel function in female constipation-predominant irritable bowel syndrome patients."