Nitazoxanide Alinia

Ball-and-Stick Model

Ball-and-Stick Model

Space-filling Model

Space-filling Model

= Carbon = Hydrogen M = Oxygen = Nitrogen = Sulfur

Year of discovery: 1975 (Romark Laboratories); Year of introduction: 1996 (in Latin America), 2002 (in US); Drug category: Thiazolide antiparasitic agent; Main uses: For the treatment of both intestinal protozoal and helminthic infections (e.g., Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica) that cause diarrhea; Related drugs. Tizoxanide, Metronidazole (Flagyl), Tinidazole.

Nitazoxanide, an antiparasitic agent of the thiazolide class, is the first approved drug for the treatment of Cryptosporidium parvum-induced diarrhea and the first new drug in 40 years for the treatment of intestinal infections caused by Giardia intestinalis.1 It contains both nitrothiazole (red) and salicylic acid (green) subunits.

Intestinal parasitic infections are the leading cause of death worldwide (ca. 3 million each year), especially in third world countries where sanitation is lacking. Protozoal parasites can be transmitted to uninfected humans by the ingestion of contaminated food and water or by contact with insects, small mammals or other humans. Immunocompromized individuals, the elderly and very young are at increased risk of infection. Two of these diseases, crypto-sporidiosis and giardiasis, are the most common protozoal infections in the US. Giardiasis, caused by the protozoan Giardia intestinalis, is spread via the fecal-oral route and as a result, children in day care facilities, hospitalized individuals and male homosexuals are at highest risk. Cryptosporidiosis, which causes diarrhea in both animals and humans, is spread by the ingestion of fecally contaminated water and affects travelers, children at day care centers, and those with a weakened immune system. In the developing world, cryptosporidiosis is the main cause of persistent diarrhea and malnutrition in children.

Nitazoxanide, first prepared in 1975, was found to be effective against intestinal tapeworms in animals during the 1980s. Subsequent testing demonstrated that nitazoxanide is a potent inhibitor of over 200

Gram-positive and Gram-negative anaerobic and Gram-positive aerobic microbes.

Nitazoxanide was approved for use in Latin American countries in 1996. In 2002, It entered the US market as an oral suspension (Aliniaâ„¢, Romark Laboratories) for the treatment of cryptosporidiosis in both adults and children. The current three-day treatment with nitazoxanide (500 mg every 12 hours for adults, 100-200 mg every 12 hours for children) significantly reduces diarrhea and results in the clearance of the microbe. Side effects are rare and usually mild. It has also been shown that treatment for three days with nitazoxanide can substantially reduce the duration of severely dehydrating, rotavirus-caused diarrhea in children.2

Nitazoxanide acts by inhibiting the parasitic enzyme pyruvate-ferredoxin oxido-reductase which plays a crucial role in anaerobic energy metabolism. After absorption, nitazoxanide is rapidly converted to the active form of the antibiotic, tizoxanide, by hydrolytic cleavage of the acetyl group (CH3CO; shown in blue above).3

Tizoxanide

Tizoxanide

Other available antiprotozoal medications (e.g., metronidazole; see page 142) are somewhat toxic at therapeutic doses and may also be ineffective due to the emergence of resistant strains of the parasite.

1. Clin. Infect. Dis. 2005, 40, 1173-1180; 2. Lancet 2006, 368, 124-129; 3. Int. J. Clin. Pharmacol. Ther 2000, 38, 387394; Refs. p. 179

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