You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameNitazoxanide
Accession NumberDB00507  (APRD00558)
TypeSmall Molecule
GroupsApproved, Investigational
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
Synonyms
SynonymLanguageCode
AdrovetNot AvailableIS
AliniaNot AvailableNot Available
NitaxozanidGermanINN
NitaxozanideFrenchINN
NitazoxanidaSpanishINN
NitazoxanidumLatinINN
NodikNot AvailableIS
OmniparaxNot AvailableIS
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aliniapowder, for suspension100 mg/5mLoralLupin Pharma2013-10-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Aliniatablet500 mgoralRomark Laboratories, LC2004-07-21Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Aliniapowder, for suspension100 mg/5mLoralRomark Laboratories, LC2002-11-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
Alpex NizoxAlpex Pharmaceutical
ANNITAAlpex Pharmaceutical
AzoxanidG&R
CelectanFarma
ColufaseRoemmers
ColuquimQuilab
DaxonSiegfried
DianideGeneral Pharma
DiarACI
FamidoxLafrancol
KasideLafrancol
KazideLafrancol
LarvisolArmofar
LumbrisFarmedic
MixelCalifornia
NiazidApex
NitaxDelta
NitaxideBeximco
NitazetGlenmark
NitazofinBussié
Brand mixtures
Brand NameIngredients
Armbid-NTNitazoxanide and Ofloxacin
Bacter-NZNitazoxanide and Ofloxacin
FlagynorNitazoxanide and Ofloxacin
Inflobid-NXTNitazoxanide and Ofloxacin
Nitazet-ONitazoxanide and Ofloxacin
Nitzix-ONitazoxanide and Ofloxacin
Nizonide-ONitazoxanide and Ofloxacin
SaltsNot Available
Categories
CAS number55981-09-4
WeightAverage: 307.282
Monoisotopic: 307.026291103
Chemical FormulaC12H9N3O5S
InChI KeyYQNQNVDNTFHQSW-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)
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as salicylamides. These are carboxamide derivatives of salicylic acid. Salicylic acid is the ortho-hydroxylated derivative of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentSalicylamides
Alternative Parents
Substituents
  • N-arylamide
  • Salicylamide
  • Phenol ester
  • Benzamide
  • Nitrothiazole
  • Benzoyl
  • 2,5-disubstituted 1,3-thiazole
  • Heteroaromatic compound
  • Acetate salt
  • Thiazole
  • Azole
  • Organic nitro compound
  • Secondary carboxylic acid amide
  • Organic nitrite
  • C-nitro compound
  • Carboxylic acid ester
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor 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.
PharmacodynamicsNitazoxanide 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 actionThe 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.
AbsorptionThe 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 distributionNot Available
Protein bindingVery 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.

SubstrateEnzymesProduct
Nitazoxanide
Not Available
Desacetyl-nitazoxanideDetails
Nitazoxanide
Not Available
Tizoxanide glucuronideDetails
Route of eliminationTizoxanide 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 life3.5 hours in patients with normal renal function
ClearanceNot Available
ToxicityIn 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9045
Blood Brain Barrier+0.7175
Caco-2 permeable-0.5571
P-glycoprotein substrateNon-substrate0.7978
P-glycoprotein inhibitor INon-inhibitor0.8874
P-glycoprotein inhibitor IINon-inhibitor0.9836
Renal organic cation transporterNon-inhibitor0.9228
CYP450 2C9 substrateNon-substrate0.7438
CYP450 2D6 substrateNon-substrate0.8431
CYP450 3A4 substrateNon-substrate0.5596
CYP450 1A2 substrateNon-inhibitor0.6339
CYP450 2C9 substrateInhibitor0.6655
CYP450 2D6 substrateNon-inhibitor0.9027
CYP450 2C19 substrateNon-inhibitor0.6341
CYP450 3A4 substrateInhibitor0.6669
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5635
Ames testAMES toxic0.8322
CarcinogenicityNon-carcinogens0.7746
BiodegradationReady biodegradable0.5458
Rat acute toxicity1.7902 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9283
hERG inhibition (predictor II)Non-inhibitor0.9295
Pharmacoeconomics
Manufacturers
  • Romark laboratories
Packagers
Dosage forms
FormRouteStrength
Powder, for suspensionoral100 mg/5mL
Tabletoral500 mg
Prices
Unit descriptionCostUnit
Alinia 500 mg tablet23.22USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States53875981995-02-072012-02-07
United States59655901997-07-032017-07-03
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point202 °CNot Available
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00755 mg/mLALOGPS
logP2.14ALOGPS
logP2.12ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)8.3ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area114.11 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity73.89 m3·mol-1ChemAxon
Polarizability27.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3950351
General Reference
  1. Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. Pubmed
External Links
ATC CodesP01AX11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (150 KB)
MSDSDownload (57.4 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Pyruvate-flavodoxin oxidoreductase

Kind: protein

Organism: Desulfovibrio africanus

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Pyruvate-flavodoxin oxidoreductase P94692 Details

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24