tizoxanide

Nitazoxanide is a new thiazolide antiparasitic agent that shows excellent in vitro activity against a wide variety of protozoa and helminths. In 1993, Dr. Jean-François Rossignol and investor/partner Marc Ayers co-founded Romark Laboratories, L.C., to develop Rossignol's invention, nitazoxanide, as a treatment for Cryptosporidium infection and to discover and develop other new small molecule drugs in the same class called the thiazolides. In 2002, Alinia® (nitazoxanide) suspension was approved by the FDA for treating diarrhea caused by Cryptosporidium parvum and Giardia lamblia in children. Alinia® tablets were approved by the FDA in July 2004. It is given by the oral route with good bioavailability and is well tolerated, with primarily mild gastrointestinal side effects. Following oral administration in humans, nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide). Tizoxanide then undergoes conjugation, primarily by glucuronidation. The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Studies have shown that the PFOR enzyme from Giardia lamblia directly reduces nitazoxanide by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of Cryptosporidium parvum appears to be similar to that of Giardia lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity. — NCATS