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Identification
NameNitazoxanide
Accession NumberDB00507  (APRD00558)
TypeSmall Molecule
GroupsApproved, Investigational, Vet Approved
DescriptionNitazoxanide, 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
Adrovet
Alinia
Nitaxozanid
Nitaxozanide
Nitazoxanida
Nitazoxanidum
Nodik
Omniparax
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AliniaPowder, for suspension100 mg/5mLOralLupin Pharma2013-10-09Not applicableUs
AliniaTablet500 mg/1OralRomark Laboratories, L.C.2004-07-21Not applicableUs
AliniaPowder, for suspension100 mg/5mLOralRomark Laboratories, L.C.2002-11-22Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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 mixturesNot Available
SaltsNot Available
Categories
UNIISOA12P041N
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
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.
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Pyruvate synthaseProteinyes
inhibitor
Desulfovibrio africanusP94692 details
Related Articles
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
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available
References
Synthesis Reference

DrugSyn.org

US3950351
General References
  1. Authors unspecified: Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. [PubMed:15504227 ]
External Links
ATC CodesP01AX11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (150 KB)
MSDSDownload (57.4 KB)
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 inhibitorInhibitor0.6655
CYP450 2D6 inhibitorNon-inhibitor0.9027
CYP450 2C19 inhibitorNon-inhibitor0.6341
CYP450 3A4 inhibitorInhibitor0.6669
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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Romark laboratories
Packagers
Dosage forms
FormRouteStrength
Powder, for suspensionOral100 mg/5mL
TabletOral500 mg/1
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5387598 No1995-02-072012-02-07Us
US5965590 No1997-07-032017-07-03Us
US5968961 No1997-05-072017-05-07Us
US6117894 No1997-05-072017-05-07Us
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
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
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

Targets

Kind
Protein
Organism
Desulfovibrio africanus
Pharmacological action
yes
Actions
inhibitor
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:
por
Uniprot ID:
P94692
Molecular Weight:
133679.405 Da
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:17158936 ]
  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. doi: 10.1016/j.bmcl.2010.04.126. Epub 2010 May 18. [PubMed:20488706 ]
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Drug created on June 13, 2005 07:24 / Updated on December 03, 2016 02:45