Napo Pharmaceuticals

crofelemer

Crofelemer Mechanism of Action

Crofelemer has a well-documented, novel anti-secretory mechanism of action which reduces excess chloride ion secretion via the CFTR channel. At a functional level, diarrhea is often associated with increased intestinal secretion. The chloride channel CFTR regulates water balance in the intestines through control of chloride ion secretion and sodium absorption. Increased chloride ion secretion, which causes excess fluid in the intestines, can be caused by bacterial toxins, serotonin, inflammatory mediators, and several drugs.

In vitro and in vivo studies of crofelemer have shown that crofelemer inhibits chloride ion secretion and reduces gastrointestinal fluid accumulation by blocking chloride ion efflux through the CFTR channel. Crofelemer does not affect gut motility and is not absorbed systemically to any significant level, two important characteristics associated with the product's demonstrated safety profile and suitability for chronic administration.

Based on its mechanism of action, i.e. blocking chloride ion secretion through CFTR, CRO-ID was investigated as an agent for the treatment of secretory diarrhea. Since crofelemer specifically blocks the mechanism by which many bacterial toxins produce diarrhea, it is ideally suited to treat the secretory diarrhea produced by acute bacterial infections (traveler's diarrhea and cholera infection). Crofelemer also targets the primary cause of secretory diarrhea associated with some drugs, specifically those used to treat HIV/AIDS. HIV protease inhibitors produce secretory diarrhea by increasing chloride ion secretion in intestinal cells.

This mechanism of action and safety profile provide a strong rationale for treatment of diarrhea in children, for whom there are currently only limited therapeutic options.

Diagram of secretion of fluid in human intestinal cells