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
External IDs
CP-12,574 / CP-12574
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TindamaxTablet, film coated250 mg/1OralMission Pharmacal2004-05-17Not applicableUs
TindamaxTablet, film coated500 mg/1OralMission Pharmacal2004-05-17Not applicableUs
TindamaxTablet, film coated500 mg/1OralPhysicians Total Care, Inc.2010-08-23Not applicableUs
TindamaxTablet, film coated500 mg/1OralDepartment Of State Health Services, Pharmacy Branch2016-11-17Not applicableUs
TinidazoleTablet500 mg/1OralBiocomp Pharma, Inc.2012-06-07Not applicableUs
TinidazoleTablet250 mg/1OralBiocomp Pharma, Inc.2012-06-07Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TindazoleTablet, film coated250 mg/1OralPack Pharmaceuticals LLC2013-10-09Not applicableUs
TindazoleTablet, film coated500 mg/1OralPack Pharmaceuticals LLC2013-10-09Not applicableUs16571 0215 22 nlmimage10 4d4326f9
TinidazoleTablet, film coated250 mg/1OralWest Ward Pharmaceutical2012-04-30Not applicableUs
TinidazoleTablet500 mg/1OralIngenus Pharmaceuticals Nj, Llc2015-08-10Not applicableUs
TinidazoleTablet500 mg/1OralNovel Laboratories, Inc.2012-04-30Not applicableUs
TinidazoleTablet250 mg/1OralGavis Pharmaceuticals, LLC.2012-04-30Not applicableUs
TinidazoleTablet, film coated500 mg/1OralWest Ward Pharmaceutical2012-04-30Not applicableUs00054 0348 07 nlmimage10 393d1c98
TinidazoleTablet250 mg/1OralEdenbridge Pharmaceuticals Llc2015-08-10Not applicableUs
TinidazoleTablet500 mg/1OralGavis Pharmaceuticals, LLC.2012-04-30Not applicableUs
TinidazoleTablet250 mg/1OralNovel Laboratories, Inc.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.

Structured Indications
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
DrugInteractionDrug group
AmiodaroneThe metabolism of Tinidazole can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Tinidazole can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Tinidazole can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Tinidazole can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of Tinidazole can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Tinidazole can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Tinidazole can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Tinidazole can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Tinidazole can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Tinidazole can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Tinidazole can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Tinidazole can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Tinidazole can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Tinidazole can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Tinidazole can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Tinidazole can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Tinidazole can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Tinidazole can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Tinidazole can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Tinidazole can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Tinidazole can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of Tinidazole can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Tinidazole can be decreased when combined with Diltiazem.Approved
DisulfiramThe risk or severity of adverse effects can be increased when Tinidazole is combined with Disulfiram.Approved
DoxycyclineThe metabolism of Tinidazole can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Tinidazole can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Tinidazole can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Tinidazole can be decreased when combined with Erythromycin.Approved, Vet Approved
EthanolThe risk or severity of adverse effects can be increased when Tinidazole is combined with Ethanol.Approved
FluconazoleThe metabolism of Tinidazole can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Tinidazole can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Tinidazole can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Tinidazole can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Tinidazole can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Tinidazole can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Tinidazole can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Tinidazole can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Tinidazole can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Tinidazole can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Tinidazole can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Tinidazole can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Tinidazole can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Tinidazole can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Tinidazole can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Tinidazole can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Tinidazole can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Tinidazole can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Tinidazole can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Tinidazole can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Tinidazole can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Tinidazole can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Tinidazole can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Tinidazole can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Tinidazole can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Tinidazole can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Tinidazole can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Tinidazole can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Tinidazole can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Tinidazole can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Tinidazole can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Tinidazole can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Tinidazole can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Tinidazole can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Tinidazole can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Tinidazole can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Tinidazole can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Tinidazole can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Tinidazole can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Tinidazole can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Tinidazole can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Tinidazole can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Tinidazole can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Tinidazole can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Tinidazole can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Tinidazole can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Tinidazole can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Tinidazole can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Tinidazole can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Tinidazole can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Tinidazole can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Tinidazole can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Tinidazole can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not 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
Human Metabolome Database
HMDB15047
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
P01AB02 — TinidazoleJ01RA11 — Ciprofloxacin and tinidazoleJ01RA13 — Norfloxacin and tinidazoleJ01XD02 — TinidazoleA02BD09 — Lansoprazole, clarithromycin and tinidazole
AHFS Codes
Not Available
PDB Entries
Not Available
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 / Triple Therapy1
4Not Yet RecruitingTreatmentHelicobacter Pylori Gastrointestinal Tract Infection1
4RecruitingTreatmentGiardiasis1
Not AvailableUnknown StatusPreventionHysterectomy1
Not AvailableUnknown StatusTreatmentAbdominal Pain (AP) / Bloating / Chronic Functional Diarrhea1

Pharmacoeconomics

Manufacturers
  • Mission pharmacal co
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral500 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 chemical entities known as nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organoheterocyclic compounds
Sub Class
Azoles
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 ]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:48