Thiabendazole

Identification

Summary

Thiabendazole is a benzimidazole used in the treatment of strongyloides, cutaneous larva migrans, visceral larva migrans, and trichinosis infections.

Generic Name
Thiabendazole
DrugBank Accession Number
DB00730
Background

2-Substituted benzimidazole first introduced in 1962. It is active against a variety of nematodes and is the drug of choice for strongyloidiasis. It has CNS side effects and hepatototoxic potential. (From Smith and Reynard, Textbook of Pharmacology, 1992, p919)

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 201.248
Monoisotopic: 201.036067929
Chemical Formula
C10H7N3S
Synonyms
  • 2-(1,3-thiazole-4-yl)-1H-benzimidazole
  • 2-(4-thiazolyl)-1H-benzimidazole
  • 2-(thiazol-4-yl)benzimidazole
  • 4-(2-benzimidazolyl)thiazole
  • TBDZ
  • Thiabendazole
  • Tiabendazol
  • Tiabendazole
  • Tiabendazolum
External IDs
  • MK 360
  • MK-360
  • NSC-525040
  • NSC-90507

Pharmacology

Indication

For the treatment of strongyloidiasis (threadworm), cutaneous larva migrans (creeping eruption), visceral larva migrans, and trichinosis.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Thiabendazole is a fungicide and parasiticide. Thiabendazole is also a chelating agent, which means that it is used medicinally to bind metals in cases of metal poisoning, such as lead poisoning, mercury poisoning or antimony poisoning. Thiabendazole is vermicidal and/or vermifugal against Ascaris lumbricoides ("common roundworm"), Strongyloides stercoralis (threadworm), Necator americanus, Ancylostoma duodenale (hookworm), Trichuris trichiura (whipworm), Ancylostoma braziliense (dog and cat hookworm), Toxocara canis, Toxocara cati (ascarids), and Enterobius vermicularis (pinworm). Thiabendazole also suppresses egg and/or larval production and may inhibit the subsequent development of those eggs or larvae which are passed in the feces.

Mechanism of action

The precise mode of action of thiabendazole on the parasite is unknown, but it most likely inhibits the helminth-specific enzyme fumarate reductase.

TargetActionsOrganism
AFumarate reductase flavoprotein subunit
inhibitor
Escherichia coli (strain K12)
Absorption

Rapidly absorbed and peak plasma concentration is reached within 1 to 2 hours after the oral administration of a suspension. Some systemic absorption may occur from topical preparations applied to the skin.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic. Metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.

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Route of elimination

It is metabolized almost completely to the 5-hydroxy form which appears in the urine as glucuronide or sulfate conjugates.

Half-life

The half-life for thiabendazole in both normal and anephric patients is 1.2 hours (range 0.9 to 2 hours). The half-life for the 5-hydroxythiabendazole metabolite in both normal and anephric patients is 1.7 hours (range 1.4 to 2 hours).

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Overdosage may be associated with transient disturbances of vision and psychic alterations. The oral LD 50 is 3.6 g/kg, 3.1 g/kg and 3.8 g/kg in the mouse, rat, and rabbit respectively.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThiabendazole may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Thiabendazole can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Thiabendazole can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Thiabendazole can be increased when it is combined with Abiraterone.
AceclofenacAceclofenac may decrease the excretion rate of Thiabendazole which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Thiabendazole which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Thiabendazole.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Thiabendazole.
AcetazolamideAcetazolamide may increase the excretion rate of Thiabendazole which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Thiabendazole which could result in a higher serum level.
Interactions
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Food Interactions
Not Available

Products

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International/Other Brands
Equizole / Thibenzole
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MintezolSuspension500 mg/5mLOralMerck Sharp & Dohme Limited1967-04-212003-03-31US flag
MintezolTablet, chewable500 mg/1OralMerck Sharp & Dohme Limited1967-04-072008-10-31US flag
Mintezol Chewable Tab 500mgTablet500 mg / tabOralMerck Sharp & Dohme Limited1969-12-312000-08-03Canada flag

Categories

ATC Codes
D01AC06 — TiabendazoleP02CA02 — Tiabendazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Benzenoids / Thiazoles / Imidazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzimidazole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Organic nitrogen compound / Organonitrogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
1,3-thiazole, ring assembly, benzimidazoles, benzimidazole fungicide (CHEBI:45979) / Thiazole fungicides (C07131) / a small molecule (THIABENDAZOLE)
Affected organisms
  • Roundworms, hookworms, and other helminth species

Chemical Identifiers

UNII
N1Q45E87DT
CAS number
148-79-8
InChI Key
WJCNZQLZVWNLKY-UHFFFAOYSA-N
InChI
InChI=1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13)
IUPAC Name
2-(1,3-thiazol-4-yl)-1H-1,3-benzodiazole
SMILES
N1C2=CC=CC=C2N=C1C1=CSC=N1

References

Synthesis Reference

Lynn E. Applegate, Carl A. Renner, "Preparation of high purity thiabendazole." U.S. Patent US5310923, issued October, 1977.

US5310923
General References
Not Available
Human Metabolome Database
HMDB0014868
KEGG Drug
D00372
KEGG Compound
C07131
PubChem Compound
5430
PubChem Substance
46505131
ChemSpider
5237
BindingDB
50121347
RxNav
10450
ChEBI
45979
ChEMBL
CHEMBL625
ZINC
ZINC000000073711
Therapeutic Targets Database
DAP000664
PharmGKB
PA164746466
PDBe Ligand
TMG
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tiabendazole
PDB Entries
1yvm / 3sfe
FDA label
Download (428 KB)
MSDS
Download (73.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Merck and co inc
Packagers
  • Dept Health Central Pharmacy
  • Medisca Inc.
  • Merck & Co.
  • Mississippi State Dept Health
Dosage Forms
FormRouteStrength
SuspensionAuricular (otic)
SuspensionOral500 mg/5mL
Tablet, chewableOral500 mg/1
TabletOral500 mg / tab
TabletOral
Prices
Unit descriptionCostUnit
Thiabendazole powder1.27USD g
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)300 °CPhysProp
water solubility50 mg/L (at 25 °C)WAUCHOPE,RD ET AL. (1991A)
logP2.47NIELSEN,LS ET AL. (1992)
pKa4.64 (at 25 °C)CHAMBERLAIN,K ET AL. (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.138 mg/mLALOGPS
logP2.47ALOGPS
logP2.33ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)10.28ChemAxon
pKa (Strongest Basic)4.08ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.91 m3·mol-1ChemAxon
Polarizability21.02 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9473
Caco-2 permeable-0.6733
P-glycoprotein substrateNon-substrate0.7174
P-glycoprotein inhibitor INon-inhibitor0.9299
P-glycoprotein inhibitor IINon-inhibitor0.9317
Renal organic cation transporterNon-inhibitor0.8624
CYP450 2C9 substrateNon-substrate0.8768
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.8103
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.5658
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8216
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6773
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9331
BiodegradationNot ready biodegradable0.9814
Rat acute toxicity2.0170 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9838
hERG inhibition (predictor II)Non-inhibitor0.9321
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.42 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0uk9-6960000000-9a4ba4c366b41681668e
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 , negativeLC-MS/MSsplash10-0fk9-0950000000-6e07d9ba69360948a837
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ufr-0690000000-b40f55bf077dd879267e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0059-0900000000-8eaacf527845d1846336
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-869b5011abd24f891c6f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-9f0e2f0e1206b841ba24
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-0b0912c87b5641d927e6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-79b8ef228f8ea67df5df
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ufr-0590000000-79f15636fdcbfb8f2fde
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fb9-0930000000-6c1cb6f8999732f4dfc8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0059-1900000000-f8df5dacb9aa1e2f51d2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0090000000-9815589c9344d01433c0
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0090000000-6ec36e16db37eb084c0b
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0490000000-80b3519b526efe662007
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0059-1910000000-679a1a2e18fa97997809
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-4900000000-a1599bcbfe1fe550efc3
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0ufr-0960000000-5883b4d0eb99d9d44922
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ufr-1890000000-8fc66231bbe9a337b27b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-003r-2900000000-74f0c0bb9208bc4125be
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0190000000-89886baf5cc3c9c2ac6d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0fb9-0940000000-3a34cc78ddd0baa309a4
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0090000000-08f3c097ab8d1eebaf7d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-f10752ce7ad55a656f25
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0490000000-28b2ba204a99953651a7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-3980000000-7bd9b16546f64d0a8a5d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fc0-3920000000-89ca28c4332f4fadea8a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-ffecb72fd0fc3f5f22e7
13C NMR Spectrum1D NMRNot Applicable

Targets

Drugtargets2
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Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Succinate dehydrogenase activity
Specific Function
Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; the fumarate reductase is used in anaerobic growth, and the succina...
Gene Name
frdA
Uniprot ID
P00363
Uniprot Name
Fumarate reductase flavoprotein subunit
Molecular Weight
65971.215 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Ge Z, Feng Y, Dangler CA, Xu S, Taylor NS, Fox JG: Fumarate reductase is essential for Helicobacter pylori colonization of the mouse stomach. Microb Pathog. 2000 Nov;29(5):279-87. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [Article]
  2. Bapiro TE, Sayi J, Hasler JA, Jande M, Rimoy G, Masselle A, Masimirembwa CM: Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans. Eur J Clin Pharmacol. 2005 Nov;61(10):755-61. doi: 10.1007/s00228-005-0037-3. Epub 2005 Oct 29. [Article]
  3. Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. [Article]
  4. Coulet M, Dacasto M, Eeckhoutte C, Larrieu G, Sutra JF, Alvinerie M, Mace K, Pfeifer AM, Galtier P: Identification of human and rabbit cytochromes P450 1A2 as major isoforms involved in thiabendazole 5-hydroxylation. Fundam Clin Pharmacol. 1998;12(2):225-35. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Delescluse C, Ledirac N, Li R, Piechocki MP, Hines RN, Gidrol X, Rahmani R: Induction of cytochrome P450 1A1 gene expression, oxidative stress, and genotoxicity by carbaryl and thiabendazole in transfected human HepG2 and lymphoblastoid cells. Biochem Pharmacol. 2001 Feb 15;61(4):399-407. [Article]
  2. Backlund M, Weidolf L, Ingelman-Sundberg M: Structural and mechanistic aspects of transcriptional induction of cytochrome P450 1A1 by benzimidazole derivatives in rat hepatoma H4IIE cells. Eur J Biochem. 1999 Apr;261(1):66-71. doi: 10.1046/j.1432-1327.1999.00225.x. [Article]

Drug created on June 13, 2005 13:24 / Updated on April 20, 2021 00:38