Safety and Efficacy of Ulimorelin Administered Postoperatively to Accelerate Recovery of Gastrointestinal Motility Following Partial Bowel Resection

Abstract

Although the efficacy of ulimorelin in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous ulimorelin at doses of 160 µg/kg and 480 µg/kg was generally well tolerated in postcolectomy patients. Similar to other promotility agents, ulimorelin may find an application in other indications better suited to its attributes.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery

“…To date, the efficacy of several ghrelin analogs (TZP-101, ulimorelin, ipamorelin) have been assessed by randomized trials in post-colectomy patients but have not been shown to be effective for reducing POGD. [119][120][121] Given the societal costs of POGD, pharmaceutical companies will continue their quest to develop an effective small and large bowel prokinetic enteric neuroendocrine peptides.…”

Brain peptides and the modulation of postoperative gastric ileus

“…In line with the assumption of a causal role of ghrelin for the observed changes after surgery, the intravenous injection of ghrelin or GRLN agonists reversed the surgery-induced delay of gastric emptying in rodents [31, 32] and humans [33] and accelerated the time to the first bowel movement in humans [33] resulting in a shorter hospitalization period [34] (Table 1). However, a recent randomized, placebo-controlled phase 3 trial investigating the effect of intravenously injected ulimorelin, a GRLN agonist, did not detect differences in the time to the first bowel movement after surgery compared to placebo [35]. Whether this is related to the dose or pharmacokinetic of the compound will have to be further established.…”

Growth hormone secretagogues: history, mechanism of action, and clinical development

“…Based on the favourable effects of ulimorelin on gastrointestinal function in animal experiments and small clinical studies, ulimorelin has progressed to randomized clinical trials for the treatment of diabetic gastroparesis or POI. In patients with diabetic gastroparesis, ulimorelin improved gastrointestinal symptoms such as vomiting and appetite loss, while there were no significant differences in improvement of gastrointestinal function between patients with POI taking ulimorelin and those taking placebo . Because of this insufficient efficacy and the risk of unexpected hypotension, its development for gastrointestinal indications has been discontinued …”

“…In patients with diabetic gastroparesis, ulimorelin improved gastrointestinal symptoms such as vomiting and appetite loss, 31 while there were no significant differences in improvement of gastrointestinal function between patients with POI taking ulimorelin and those taking placebo. 68 Because of this insufficient efficacy and the risk of unexpected hypotension, 32 its development for gastrointestinal indications has been discontinued. 69 Relamorelin A Phase I clinical trial showed that relamorelin, compared with placebo, greatly accelerated gastric emptying in female patients with diabetic gastroparesis.…”