Methods and Findings in Experimental and Clinical Pharmacology
Vol. 25, Suppl. A, 2003
ISSN 0379-0355
Copyright 2003 Prous Science, S.A.
CCC: 0379-0355/2003
http://www.prous.com

Racecadotril

R. Lozano Fernández de Pinedo

Ferrer Grupo, Barcelona, Spain

Racecadotril is an antidiarrheal drug with an original mechanism of action: the inhibition of enkephalinase. This produces an increase in the levels of enkephalins that act on the enterocyte, thus inhibiting hypersecretion.

Experimental and clinical studies have shown that racecadotril inhibits intestinal secretion induced by chemical or microbiological agents, without slowing gastrointestinal transit. Cholera toxin was used to induce intestinal secretion in a model employing segmental perfusion of the human proximal jejunum. Significant water secretion was induced in a control group (131 ml/30 cm.h.), but prior administration of racecadotril completely prevented this secretion by leaving an absorption rate of 27 ml/30 cm.h. Intestinal electrolyte transport was also significantly changed towards absorption by racecadotril

In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity in newborn gnotobiotic piglets. In humans, racecadotril has no effects on the central nervous system, and, contrary to loperamide, it can be administered in children of less than two years.

After oral administration, racecadotril is rapidly absorbed and entirely metabolized to its active metabolite thiorphan. The activity on plasmatic enkephalinase appears 30 min after the administration. The peak plasma concentration of thiorphan is reached 60 min after administration of a single oral dose of racecadotril. The biological half-life of enkephalinase activity is 3 h.

In adults, adequate plasmatic levels are maintained with the administration of 100 mg of racecadotril every 8 h, and are not modified by repeated administration or in aged patients. A pharmacokinetics study in children indicated that the administration of 1.5 mg/kg of racecadotril every 8 h is adequate.

Clinical trials have shown that racecadotril is effective in acute diarrhea, with beneficial effects on its duration, as well as in the frequency and weight of stools. It is noteworthy that placebo-controlled studies in children have shown that the needed amount of oral rehydration diminishes with the administration of racecadotril.

Comparative studies versus loperamide have shown that patients receiving racecadotril have a significantly lower incidence of abdominal distention and secondary constipation. This is attributable to the fact that racecadotril does not slow gastrointestinal transit.

Placebo-controlled studies have shown that the incidence of adverse events is similar, and that these correspond to the usual symptoms of diarrhea.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 25, Suppl. A, 2003
ISSN 0379-0355 Copyright 2003 Prous Science, S.A. CCC: 0379-0355/2003 http://www.prous.com