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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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
FasigynNot Available
TindamaxNot Available
TindazoleNot Available
Brand mixturesNot Available
Categories
CAS number19387-91-8
WeightAverage: 247.272
Monoisotopic: 247.062676609
Chemical FormulaC8H13N3O4S
InChI KeyHJLSLZFTEKNLFI-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassImidazoles
Direct parentNitroimidazoles
Alternative parentsTrisubstituted Imidazoles; N-substituted Imidazoles; Sulfones; Sulfoxides; Nitro Compounds; Nitronic Acids; Organic Oxoazanium Compounds; Polyamines
Substituentsn-substituted imidazole; sulfone; sulfonyl; nitronic acid; nitro compound; sulfoxide; organic oxoazanium; polyamine; organonitrogen compound; amine
Classification descriptionThis compound belongs to the nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.975
Blood Brain Barrier + 0.9308
Caco-2 permeable - 0.6003
P-glycoprotein substrate Substrate 0.6257
P-glycoprotein inhibitor I Non-inhibitor 0.7815
P-glycoprotein inhibitor II Non-inhibitor 0.9706
Renal organic cation transporter Non-inhibitor 0.8178
CYP450 2C9 substrate Non-substrate 0.7946
CYP450 2D6 substrate Non-substrate 0.8931
CYP450 3A4 substrate Substrate 0.5149
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.876
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7518
Ames test AMES toxic 0.9106
Carcinogenicity Non-carcinogens 0.5986
Biodegradation Not ready biodegradable 0.7608
Rat acute toxicity 2.1458 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.5582
hERG inhibition (predictor II) Non-inhibitor 0.5554
Pharmacoeconomics
Manufacturers
  • Mission pharmacal co
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Tindamax 500 mg tablet9.02USDtablet
Tinidazole 500 mg tablet4.73USDtablet
Tindamax 250 mg tablet3.25USDtablet
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 solubility3.03e+00 g/lALOGPS
logP-0.41ALOGPS
logP-0.58ChemAxon
logS-1.9ALOGPS
pKa (strongest basic)3.1ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count0ChemAxon
polar surface area97.78ChemAxon
rotatable bond count5ChemAxon
refractivity57.66ChemAxon
polarizability23.27ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Link
  2. Lopez Nigro MM, Carballo MA: Genotoxicity and cell death induced by tinidazole (TNZ). Toxicol Lett. 2008 Jul 30;180(1):46-52. Epub 2008 Jun 5. Pubmed
  3. Fung HB, Doan TL: Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther. 2005 Dec;27(12):1859-84. Pubmed
External Links
ResourceLink
KEGG DrugD01426
PubChem Compound5479
PubChem Substance46506396
ChemSpider5279
PharmGKBPA10813
Drugs.comhttp://www.drugs.com/cdi/tinidazole.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tin1701.shtml
WikipediaTinidazole
ATC CodesJ01XD02P01AB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(249 KB)
MSDSshow(73.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details

References:

  1. Fung HB, Doan TL: Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther. 2005 Dec;27(12):1859-84. Pubmed
  2. Lopez Nigro MM, Carballo MA: Genotoxicity and cell death induced by tinidazole (TNZ). Toxicol Lett. 2008 Jul 30;180(1):46-52. Epub 2008 Jun 5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12