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Identification
NameTinidazole
Accession NumberDB00911  (APRD01260)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A nitroimidazole antitrichomonal agent effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia infections. [PubChem]

Structure
Thumb
Synonyms
Timidazole
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tindamaxtablet, film coated250 mg/1oralMission Pharmacal Company2004-05-17Not applicableUs
Tindamaxtablet, film coated500 mg/1oralPhysicians Total Care, Inc.2010-08-23Not applicableUs
Tindamaxtablet, film coated500 mg/1oralMission Pharmacal Company2004-05-17Not applicableUs
Tinidazoletablet500 mg/1oralBiocomp Pharma, Inc.2012-06-07Not applicableUs
Tinidazoletablet250 mg/1oralBiocomp Pharma, Inc.2012-06-07Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tindazoletablet, film coated500 mg/1oralPACK Pharmaceuticals, LLC2013-10-09Not applicableUs
Tindazoletablet, film coated250 mg/1oralPACK Pharmaceuticals, LLC2013-10-09Not applicableUs
Tinidazoletablet250 mg/1oralGAVIS Pharmaceuticals, LLC2012-04-30Not applicableUs
Tinidazoletablet, film coated250 mg/1oralRoxane Laboratories, Inc2012-04-30Not applicableUs
Tinidazoletablet500 mg/1oralEdenbridge Pharmaceuticals, LLC2015-08-10Not applicableUs
Tinidazoletablet250 mg/1oralEdenbridge Pharmaceuticals, LLC2015-08-10Not applicableUs
Tinidazoletablet500 mg/1oralNovel Laboratories, Inc.2012-04-30Not applicableUs
Tinidazoletablet250 mg/1oralNovel Laboratories, Inc.2012-04-30Not applicableUs
Tinidazoletablet500 mg/1oralGAVIS Pharmaceuticals, LLC2012-04-30Not applicableUs
Tinidazoletablet, film coated500 mg/1oralRoxane Laboratories, Inc2012-04-30Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
FasigynNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII033KF7V46H
CAS number19387-91-8
WeightAverage: 247.272
Monoisotopic: 247.062676609
Chemical FormulaC8H13N3O4S
InChI KeyInChIKey=HJLSLZFTEKNLFI-UHFFFAOYSA-N
InChI
InChI=1S/C8H13N3O4S/c1-3-16(14,15)5-4-10-7(2)9-6-8(10)11(12)13/h6H,3-5H2,1-2H3
IUPAC Name
1-[2-(ethanesulfonyl)ethyl]-2-methyl-5-nitro-1H-imidazole
SMILES
CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentNitroimidazoles
Alternative Parents
Substituents
  • Trisubstituted imidazole
  • Nitroimidazole
  • 1,2,5-trisubstituted-imidazole
  • N-substituted imidazole
  • Heteroaromatic compound
  • Sulfonyl
  • Sulfone
  • Organic nitro compound
  • Organic nitrite
  • C-nitro compound
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Organosulfur compound
  • Organonitrogen compound
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of trichomoniasis caused by T. vaginalis in both female and male patients. Also for the treatment of giardiasis caused by G. duodenalis in both adults and pediatric patients older than three years of age and for the treatment of intestinal amebiasis and amebic liver abscess caused by E. histolytica in both adults and pediatric patients older than three years of age.
PharmacodynamicsTinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia duodenalis (also termed G. lamblia), and Entamoeba histolytica. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.
Mechanism of actionTinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar.
Related Articles
AbsorptionRapidly and completely absorbed under fasting conditions. Administration with food results in a delay in Tmax of approximately 2 hours and a decline in Cmax of approximately 10% and an AUC of 901.6 ± 126.5 mcg hr/mL.
Volume of distribution
  • 50 L
Protein bindingPlasma protein binding of tinidazole is 12%.
Metabolism

Hepatic, mainly via CYP3A4. Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Tinidazole is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.

Route of eliminationTinidazole crosses the placental barrier and is secreted in breast milk. Tinidazole is excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.
Half lifeElimination half-life is 13.2 ± 1.4 hours. Plasma half-life is 12 to 14 hours.
ClearanceNot Available
ToxicityThere are no reported overdoses with tinidazole in humans. In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.
Affected organisms
  • Trichomonas vaginalis, Giardia duodenalis, and Entamoeba histolytica
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.975
Blood Brain Barrier+0.9308
Caco-2 permeable-0.6003
P-glycoprotein substrateSubstrate0.6257
P-glycoprotein inhibitor INon-inhibitor0.7815
P-glycoprotein inhibitor IINon-inhibitor0.9706
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.7946
CYP450 2D6 substrateNon-substrate0.8931
CYP450 3A4 substrateSubstrate0.5149
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.876
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7518
Ames testAMES toxic0.9106
CarcinogenicityNon-carcinogens0.5986
BiodegradationNot ready biodegradable0.7608
Rat acute toxicity2.1458 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5582
hERG inhibition (predictor II)Non-inhibitor0.5554
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Mission pharmacal co
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg/1
Tabletoral500 mg/1
Tablet, film coatedoral250 mg/1
Tablet, film coatedoral500 mg/1
Prices
Unit descriptionCostUnit
Tindamax 500 mg tablet9.02USD tablet
Tinidazole 500 mg tablet4.73USD tablet
Tindamax 250 mg tablet3.25USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point127-128 °CPhysProp
water solubility1.99E+004 mg/LNot Available
logP-0.35HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility3.03 mg/mLALOGPS
logP-0.41ALOGPS
logP-0.58ChemAxon
logS-1.9ALOGPS
pKa (Strongest Basic)3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area97.78 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity57.66 m3·mol-1ChemAxon
Polarizability23.27 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Lopez Nigro MM, Carballo MA: Genotoxicity and cell death induced by tinidazole (TNZ). Toxicol Lett. 2008 Jul 30;180(1):46-52. doi: 10.1016/j.toxlet.2008.05.017. Epub 2008 Jun 5. [PubMed:18582545 ]
  2. Fung HB, Doan TL: Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther. 2005 Dec;27(12):1859-84. [PubMed:16507373 ]
  3. Link [Link]
External Links
ATC CodesA02BD09J01RA11J01RA13J01XD02P01AB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (249 KB)
MSDSDownload (73.1 KB)
Interactions
Drug Interactions
Drug
DisulfiramThe risk or severity of adverse effects can be increased when Tinidazole is combined with Disulfiram.
EthanolThe risk or severity of adverse effects can be increased when Tinidazole is combined with Ethanol.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
binder
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Fung HB, Doan TL: Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther. 2005 Dec;27(12):1859-84. [PubMed:16507373 ]
  2. Lopez Nigro MM, Carballo MA: Genotoxicity and cell death induced by tinidazole (TNZ). Toxicol Lett. 2008 Jul 30;180(1):46-52. doi: 10.1016/j.toxlet.2008.05.017. Epub 2008 Jun 5. [PubMed:18582545 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12