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Identification
Name Nitazoxanide
Accession Number DB00507 (APRD00558)
Type small molecule
Groups approved
Description

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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
2-(Acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide
2-Acetyloxy-N-[(5-nitro-2-thiazolyl)]benzamide
Nitazoxanid
Nitazoxanida [INN-Spanish]
Nitazoxanidum [INN-Latin]
Tizoxanide Glucuronide
Salts Not Available
Brand names
Name Company
Alinia
Phavic-1
Brand mixtures Not Available
Categories
  • Antiparasitic Agents
CAS number 55981-09-4
Weight Average: 307.282
Monoisotopic: 307.026291103
Chemical Formula C12H9N3O5S
InChI Key InChIKey=YQNQNVDNTFHQSW-UHFFFAOYSA-N
InChI
InChI=1S/C12H9N3O5S/c1-7(16)20-9-5-3-2-4-8(9)11(17)14-12-13-6-10(21-12)15(18)19/h2-6H,1H3,(H,13,14,17)
Plain Text
IUPAC Name
2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl acetate
SMILES
CC(=O)OC1=CC=CC=C1C(=O)NC1=NC=C(S1)[N+]([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylacetates
  • Benzamides
Substructures
  • Carboxylic Acids and Derivatives
  • Acetates
  • Oxoazaniums
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Nitro compounds
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Phenyl Esters
  • Benzamides
Pharmacology
Indication 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.
Pharmacodynamics 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.
Absorption 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
Protein binding Very High (greater than 99%), bound to proteins. Binding is not affected by degree of renal impairment.
Metabolism
Rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide), followed by conjugation, primarily by glucuronidation to tizoxanide glucuronide.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Nitazoxanide
    		Desacetyl-nitazoxanide Details
    Nitazoxanide
      		Tizoxanide glucuronide Details
      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.
      Half life 3.5 hours in patients with normal renal function
      Clearance Not Available
      Toxicity 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.
      Affected organisms
      • Protozoa
      Pathways Not Available
      Pharmacoeconomics
      Manufacturers
      • Romark laboratories
      Packagers
      Dosage forms
      Form Route Strength
      Suspension Oral
      Tablet Oral
      Prices
      Unit description Cost Unit
      Alinia 500 mg tablet 23.22 USD tablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      Country Patent Number Approved Expires (estimated)
      United States 5965590 1997-07-03 2017-07-03
      United States 5387598 1995-02-07 2012-02-07
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 202 °C Not Available
      logP 1.2 Not Available
      Predicted Properties
      Property Value Source
      water solubility 7.55e-03 g/l ALOGPS
      logP 2.14 ALOGPS
      logP 2.12 ChemAxon
      logS -4.6 ALOGPS
      pKa (strongest acidic) 8.3 ChemAxon
      pKa (strongest basic) -4.2 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 5 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 114.11 ChemAxon
      rotatable bond count 5 ChemAxon
      refractivity 73.89 ChemAxon
      polarizability 27.54 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference
      1. Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. Pubmed
      External Links
      Resource Link
      KEGG Drug D02486 Link_out
      PubChem Compound 41684 Link_out
      PubChem Substance 46507813 Link_out
      ChemSpider 38037 Link_out
      BindingDB 50182652 Link_out
      Therapeutic Targets Database DAP001293 Link_out
      PharmGKB PA164754874 Link_out
      RxList http://www.rxlist.com/cgi/generic/alinia.htm Link_out
      Drugs.com http://www.drugs.com/cdi/nitazoxanide.html Link_out
      PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ali1659.shtml Link_out
      Wikipedia http://en.wikipedia.org/wiki/Nitazoxanide Link_out
      ATC Codes
      • P01AX11
      AHFS Codes Not Available
      PDB Entries Not Available
      FDA label show (150 KB)
      MSDS show (57.4 KB)
      Interactions
      Drug Interactions Searched, but no interactions found.
      Food Interactions Not Available
      Targets

      1. Pyruvate-ferredoxin oxidoreductase

      Pharmacological action: yes
      Actions: inhibitor

      Oxidoreductase required for the transfer of electrons from pyruvate to flavodoxin, which reduces nitrogenase (By similarity)

      Organism class: bacterial
      UniProt ID: P94692 Link_out
      Gene: por
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. 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
      2. 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. Epub 2010 May 18. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19