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, racecadotril) and a mu-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.
Duval-Iflah
Y
Y
Institut National de la Recherche Agronomique, Unité d'Ecologie et de Physiologie du Système Digestif, Centre de Recherche de Jouy, Jouy-en-Josas, France. duval@biotec.jouy.inra.fr
Berard
H
H
Baumer
P
P
Guillaume
P
P
Raibaud
P
P
Joulin
Y
Y
Lecomte
J M
JM
D000818:Animals; D000831:Animals, Newborn; D000930:Antidiarrheals / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004064:Digestive System / Q000382:microbiology; D005856:Germ-Free Life; D008139:Loperamide / Q000494:pharmacology* / Q000633:toxicity; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013552:Swine; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D000930:Antidiarrheals; D011480:Protease Inhibitors; D008139:Loperamide; C049331:racecadotril; D015244:Thiorphan; D015260:Neprilysin