Identification

Name
Tinidazole
Accession Number
DB00911  (APRD01260)
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • Timidazole
  • Tinidazole
External IDs
CP-12,574 / CP-12574
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TindamaxTablet, film coated500 mg/1OralPhysicians Total Care, Inc.2010-08-23Not applicableUs
TindamaxTablet, film coated250 mg/1OralMission Pharmacal Company2004-05-17Not applicableUs
TindamaxTablet, film coated500 mg/1OralDepartment Of State Health Services, Pharmacy Branch2016-11-172017-06-23Us
TindamaxTablet, film coated500 mg/1OralMission Pharmacal Company2004-05-17Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TindazoleTablet, film coated250 mg/1OralRising Pharmaceuticals2013-10-09Not applicableUs
TindazoleTablet, film coated250 mg/1OralPack Pharmaceuticals LLC2013-10-09Not applicableUs
TindazoleTablet, film coated500 mg/1OralRising Pharmaceuticals2013-10-09Not applicableUs
TindazoleTablet, film coated500 mg/1OralPack Pharmaceuticals LLC2013-10-09Not applicableUs16571 0215 22 nlmimage10 4d4326f9
TinidazoleTablet250 mg/1OralNovel Laboratories, Inc.2012-04-30Not applicableUs
TinidazoleTablet250 mg/1OralEdenbridge Pharmaceuticals Llc2015-08-10Not applicableUs
TinidazoleTablet250 mg/1OralBiocomp Pharma, Inc.2012-06-07Not applicableUs
TinidazoleTablet250 mg/1OralIngenus Pharmaceuticals Nj, Llc2015-08-10Not applicableUs
TinidazoleTablet250 mg/1OralLupin Pharmaceuticals2012-04-30Not applicableUs
TinidazoleTablet, film coated250 mg/1OralWest-Ward Pharmaceuticals Corp.2012-04-30Not applicableUs
International/Other Brands
Fasigyn
Categories
UNII
033KF7V46H
CAS number
19387-91-8
Weight
Average: 247.272
Monoisotopic: 247.062676609
Chemical Formula
C8H13N3O4S
InChI Key
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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Tinidazole 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 action

Tinidazole 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.

TargetActionsOrganism
ADNA
binder
Human
Absorption

Rapidly 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 binding

Plasma 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 elimination

Tinidazole 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 life

Elimination half-life is 13.2 ± 1.4 hours. Plasma half-life is 12 to 14 hours.

Clearance
Not Available
Toxicity

There 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Tinidazole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Tinidazole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Tinidazole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tinidazole.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Tinidazole.
6-Deoxyerythronolide BThe metabolism of Tinidazole can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Tinidazole.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Tinidazole.
AbacavirTinidazole may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Tinidazole can be increased when combined with Abatacept.
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB0015047
KEGG Drug
D01426
PubChem Compound
5479
PubChem Substance
46506396
ChemSpider
5279
ChEBI
63627
ChEMBL
CHEMBL1220
PharmGKB
PA10813
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tinidazole
ATC Codes
J01RA13 — Norfloxacin and tinidazoleJ01RA11 — Ciprofloxacin and tinidazoleP01AB02 — TinidazoleJ01XD02 — TinidazoleG01AF20 — Combinations of imidazole derivativesA02BD09 — Lansoprazole, clarithromycin and tinidazole
FDA label
Download (249 KB)
MSDS
Download (73.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionBacterial Vaginosis (BV)1
1CompletedTreatmentTrichomoniasis1
2CompletedTreatmentMalaria caused by plasmodium vivax1
2CompletedTreatmentUrethritis1
2WithdrawnTreatmentRecurrent Bacterial Vaginosis1
3CompletedTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
3CompletedTreatmentBacterial Vaginosis (BV)1
3Unknown StatusTreatmentMalignant Neoplasm of Stomach1
4CompletedTreatmentBacterial Vaginosis (BV)1
4CompletedTreatmentHelicobacter Infection1
4Not Yet RecruitingTreatmentAntimicrobial Susceptibility Testing / Bacterial Infection Due to Helicobacter Pylori (H. Pylori)1
4Not Yet RecruitingTreatmentAntimicrobial Susceptibility Testing / Triple Therapy1
4Not Yet RecruitingTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)2
4RecruitingTreatmentGiardiasis1
4WithdrawnTreatmentHelicobacter Pylori Gastrointestinal Tract Infection1
Not AvailableRecruitingPreventionForeskin HIV Susceptibility1
Not AvailableUnknown StatusPreventionHysterectomy1
Not AvailableUnknown StatusTreatmentAbdominal Pain (AP) / Bloating / Chronic Functional Diarrhea1

Pharmacoeconomics

Manufacturers
  • Mission pharmacal co
Packagers
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • BioComp Pharma
  • Mikart Inc.
  • Mission Pharmacal
  • Novartis AG
  • PD-Rx Pharmaceuticals Inc.
  • Presutti Laboratories Inc.
Dosage forms
FormRouteStrength
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral250 mg/1
TabletOral250 mg/1
TabletOral500 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)127-128 °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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0290000000-6e567c97c2cf4ca3fd01
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0390000000-28e470db2eb20392a17a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-4910000000-8c46b903514b344ac47c

Taxonomy

Description
This compound belongs to the class of organic compounds known as nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Nitroimidazoles
Alternative Parents
Nitroaromatic compounds / 1,2,5-trisubstituted imidazoles / N-substituted imidazoles / Sulfones / Heteroaromatic compounds / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 2 more
Substituents
1,2,5-trisubstituted-imidazole / Nitroaromatic compound / Nitroimidazole / Trisubstituted imidazole / N-substituted imidazole / Sulfone / Heteroaromatic compound / Sulfonyl / C-nitro compound / Organic nitro compound
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles (CHEBI:63627)

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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:44