Effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet

Abstract

Methods The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, racecadotril) and a μ‐receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5) – nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. Conclusions In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

Pharmacologic Management of Diarrhea in Patients With Short Bowel Syndrome

“…The anatomy of the GI remnant can be a primary driver of bacterial overgrowth. For example, patients with blind loops or small‐bowel dilation have reduced intestinal motility, which can result in stagnation of intestinal contents and promote local bacterial fermentation 23 , 53 . Patients with resections that include removal of the terminal ileum and/or ileocecal valve may experience migration of anaerobic colonic bacteria into the small intestine because of a breakdown of this anatomical transition zone 54 .…”

“…Patients with resections that include removal of the terminal ileum and/or ileocecal valve may experience migration of anaerobic colonic bacteria into the small intestine because of a breakdown of this anatomical transition zone 54 . Finally, medications commonly prescribed to patients with SBS, including antimotility agents and acid‐suppressing therapies, have the potential to disrupt normal bacterial flora and permit overgrowth 23 , 53 …”

Antinociceptive potency of enkephalins and enkephalinase inhibitors in the mouse model of colorectal distension—proof‐of‐concept

“…[26] Noteworthy, racecadotril does not induce reactive constipation [27] and does not promote small bowel bacterial overgrowth, [28] actions exhibited by a widely used loperamide. Racecadotril, inhibitor of neprilysin, is an antidiarrheal agent which acts without modifying the basal absorption of water and electrolytes and with no impact on intestinal transit.…”

Racecadotril : A Novel Antidiarrheal

“…The antisecretory mechanisms are independent of effects on intestinal motility, differentiating this compound from μ-opiate receptor agonists like loperamide and diphenoxylate. Experimental studies in rodents and human volunteers demonstrated no delay on gastrointestinal transit or increase in experimental bacterial proliferation in small bowel of germ free piglets with racecadotril as compared to loperamide [5].…”