|Accession Number||DB00507 (APRD00558)|
|Groups||Approved, Investigational, Vet Approved|
Nitazoxanide, also known by the brand name Alinia, is a synthetic nitrothiazolyl-salicylamide derivative and an anti-protozoal agent. It is approved for treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older. Following oral administration it is rapidly hydrolyzed to its active metabolite, tizoxanide, which is 99% protein bound. Peak concentrations are observed 1–4 hours after administration. It is excreted in the urine, bile and feces. Untoward effects include abdominal pain, vomiting and diarrhea. [Wikipedia]
|External IDs||PH 5776|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 307.282 |
For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia and for the treatment of diarrhea in children caused by the protozoa Cryptosporidium parvum.
Nitazoxanide is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that nitazoxanide inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Nitazoxanide is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, nitazoxanide is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
|Mechanism of action|
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.
The relative bioavailability of the suspension compared to the tablet was 70%. When administered with food the AUC and Cmax increased by two-fold and 50%, respectively, for the tablet and 45 to 50% and ≤ 10%, respectively, for the oral suspension.
|Volume of distribution||Not Available|
Very High (greater than 99%), bound to proteins. Binding is not affected by degree of renal impairment.
Rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide), followed by conjugation, primarily by glucuronidation to tizoxanide glucuronide.
|Route of elimination|
Tizoxanide is excreted in the urine, bile and feces, and tizoxanide glucuronide is excreted in urine and bile. Approximately two-thirds of the oral dose of nitazoxanide is excreted in the feces and one-third in the urine.
3.5 hours in patients with normal renal function
In acute studies in rodents and dogs, the oral LD50 was higher than 10,000 mg/kg. Single oral doses of up to 4000 mg nitazoxanide have been administered to healthy adult volunteers without significant adverse effects.
|Pharmacogenomic Effects/ADRs||Not Available|
|Drug Interactions||No interactions found.|
|Food Interactions||Not Available|
|ATC Codes||P01AX11 — Nitazoxanide|
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (150 KB)|
|MSDS||Download (57.4 KB)|
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
|Predicted ADMET features|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of organic compounds known as acylsalicylamides. These are o-acylated derivatives of salicylamide.|
|Class||Benzene and substituted derivatives|
|Sub Class||Benzoic acids and derivatives|
|Alternative Parents||Phenol esters / Benzamides / Phenoxy compounds / Benzoyl derivatives / Nitroaromatic compounds / Nitrothiazoles / 2,5-disubstituted thiazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Organic zwitterions / Hydrocarbon derivatives / Organonitrogen compounds / Carbonyl compounds / Organopnictogen compounds / Organic oxides|
|Substituents||Acylsalicylamide / Phenol ester / Benzamide / Phenoxy compound / Nitroaromatic compound / Benzoyl / Nitrothiazole / 2,5-disubstituted 1,3-thiazole / Azole / Thiazole/ Heteroaromatic compound / Organic nitro compound / Secondary carboxylic acid amide / Carboxamide group / Carboxylic acid ester / C-nitro compound / Organoheterocyclic compound / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Allyl-type 1,3-dipolar organic compound / Azacycle / Carboxylic acid derivative / Organic oxoazanium / Monocarboxylic acid or derivatives / Organic nitrogen compound / Organic oxide / Organonitrogen compound / Organooxygen compound / Hydrocarbon derivative / Carbonyl group / Organopnictogen compound / Organic oxygen compound / Organic zwitterion / Aromatic heteromonocyclic compound|
|Molecular Framework||Aromatic heteromonocyclic compounds|
|External Descriptors||Not Available|
- Desulfovibrio africanus
- Pharmacological action
- General Function:
- Thiamine pyrophosphate binding
- Specific Function:
- Catalyzes the ferredoxin-dependent oxidative decarboxylation of pyruvate. Required for the transfer of electrons from pyruvate to ferredoxin (PubMed:9294422, PubMed:7612653). Ferredoxin I and ferredoxin II, which are single 4Fe-4S cluster ferredoxins are the most effective electron carriers of POR (PubMed:7612653).
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 133679.405 Da
- Hoffman PS, Sisson G, Croxen MA, Welch K, Harman WD, Cremades N, Morash MG: Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni. Antimicrob Agents Chemother. 2007 Mar;51(3):868-76. Epub 2006 Dec 11. [PubMed:17158936 ]
- Ballard TE, Wang X, Olekhnovich I, Koerner T, Seymour C, Hoffman PS, Macdonald TL: Biological activity of modified and exchanged 2-amino-5-nitrothiazole amide analogues of nitazoxanide. Bioorg Med Chem Lett. 2010 Jun 15;20(12):3537-9. doi: 10.1016/j.bmcl.2010.04.126. Epub 2010 May 18. [PubMed:20488706 ]