crofelemer

Crofelemer (USAN, trade name Mytesi) is an antidiarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri. Crofelemer treats the symptoms of disease, but it is not used to treat infectious diarrhea (diarrhea caused by infection of the digestive system by a bacterium, virus or parasite). It was initially developed by Napo Pharmaceuticals, which is a wholly owned subsidiary of Jaguar Health, Inc. A Phase III clinical trial for diarrhea in HIV patients was completed in 2012, and the drug was approved by the US Food and Drug Administration (FDA) on 31 December 2012. Mechanism of action The drug is taken orally and works by modulating cystic fibrosis transmembrane conductance regulator (CFTR) and the calcium-activated chloride channel (CaCC), two chloride ion channels from the luminal side of the gastrointestinal tract. This is a first-in-class antisecretory antidiarrheal mechanism of action and it does not affect gastrointestinal motility, unlike the traditional antimotility drugs. As a result of the channel regulation, fewer chloride ions are secreted into the gut, which decreases the associated secretion of sodium ions and accompanying water, thus improving stool consistency and reducing the frequency of watery stools and duration of the diarrhea. The mechanism is selective for the CFTR and CaCC, as other channels involved in intestinal fluid secretion, namely sodium and potassium channels, are not affected by crofelemer, nor is cAMP or calcium signaling. Crofelemer is minimally, if at all, absorbed from the gut into the bloodstream, and is mostly excreted in the stools.