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

Methods The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, racecadotri l) and a mu-receptor agonist (loperamide), on intestinal growth of a bacter ial nonpathogenic strain (Escherichia coli E 404) and on the central nervou s system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S-1) and the E . coli ratio of stomach:segment S-1 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 S-1 and the E. coli ra tio stomach:S-1 were both significantly higher than with racecadotril or co ntrol (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S-1). There were no clinical signs of neuro toxicity 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. a n equivalent high dose of loperamide (5 mg/kg b.d,) resulted in death in th ree out of four piglets. Conclusions In contrast to loperamide, racecadotril did not induce bacteria l overgrowth and did not produce central neurotoxicity.