Tioconazole

Identification

Summary

Tioconazole is an imidazole antifungal used to treat vulvovaginal candidiasis.

Brand Names
Monistat Simple Therapy, Vagistat
Generic Name
Tioconazole
DrugBank Accession Number
DB01007
Background

Tioconazole is an imidazole antifungal used to treat fungal and yeast infections. Topical formulations are used for ringworm, jock itch, athlete's foot, and tinea versicolor or "sun fungus". Tioconazole interacts with 14-alpha demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. In addition to being an antifungal, tioconazole also has antibacterial effects on certain Gram-positive cocci bacteria.1

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 387.711
Monoisotopic: 385.981416859
Chemical Formula
C16H13Cl3N2OS
Synonyms
  • Tioconazol
  • Tioconazole
  • Tioconazolum

Pharmacology

Indication

For the local treatment of vulvovaginal candidiasis (moniliasis).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofFungal skin infection••• •••••••••••• ••••••••• •••••
Treatment ofInfection mixed••• •••••••••••• ••••••••• •••••
Treatment ofOnychomycosis••• ••••••••• ••••••
Treatment ofSkin bacterial infection••• •••••••••••• ••••••••• •••••
Treatment ofVaginal candidiasis••• •••••••••••• •••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. In addition to its broad spectrum antifungal effects with tioconazole being effective against commonly occurring dermatophyte and yeast-like fungal species, tioconazole also has antibacterial effects on certain Gram-positive cocci bacteria.1

Mechanism of action

Tioconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

TargetActionsOrganism
ACytochrome P450 51
antagonist
Yeast
ULanosterol 14-alpha demethylase
inhibitor
Humans
Absorption

Systemic absorption following a single intravaginal application of tioconazole in nonpregnant patients is negligible.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Orally administered tioconazole is extensively metabolized. The major metabolites are glucuronide conjugates.

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.

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
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Tioconazole.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Tioconazole.
AcetaminophenTioconazole may increase the hepatotoxic activities of Acetaminophen.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Tioconazole.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Tioconazole.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Tioconazole hydrochlorideT1QKM21KYB61675-64-7UKQXXGSDDSCAHA-UHFFFAOYSA-N
International/Other Brands
GyneCure / Monistat 1 / Trosyd / Trosyl
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Basic Care TioconazoleOintment6.5 g/100gVaginalAmazon.com Services LLC2021-07-27Not applicableUS flag
Basic Care Tioconazole 1Ointment6.5 g/100gVaginalL. Perrigo Company2019-05-222023-04-01US flag
CareOne Tioconazole 1Ointment6.5 g/100gVaginalAmerican Sales Company2008-01-07Not applicableUS flag
Dg Health Tioconazole 1Ointment6.5 g/100gVaginalDOLGENCORP, LLC2019-03-01Not applicableUS flag
Equaline Tioconazole 1Ointment6.5 g/100gVaginalUnited Natural Foods, Inc. dba UNFI2016-03-08Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Gynecure Com.pk.vag Ont6.5%vulvar Crm1% W/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada flag
Gynecure Com.pk.vag Ont6.5%vulvar Crm1% W/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada flag
Gynecure Com.pk.vag Ovule300mg Vulv.crm1%w/wTioconazole (300 mg / kit) + Tioconazole (1 % / kit)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada flag
Gynecure Com.pk.vag Ovule300mg Vulv.crm1%w/wTioconazole (300 mg / kit) + Tioconazole (1 % / kit)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada flag
Gynecure Tandempk.vag Ont6.5%/vulv.crm1%-w/wTioconazole (1 % / kit) + Tioconazole (6.5 % / kit)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1997-03-272002-11-11Canada flag

Categories

ATC Codes
G01AF20 — Combinations of imidazole derivativesD01AC07 — TioconazoleG01AF08 — Tioconazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Dichlorobenzenes / N-substituted imidazoles / Aryl chlorides / Thiophenes / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
show 1 more
Substituents
1,3-dichlorobenzene / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzylether / Chlorobenzene / Dialkyl ether / Ether
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, thiophenes, ether, dichlorobenzene (CHEBI:77898)
Affected organisms
  • Yeast and other fungi

Chemical Identifiers

UNII
S57Y5X1117
CAS number
65899-73-2
InChI Key
QXHHHPZILQDDPS-UHFFFAOYSA-N
InChI
InChI=1S/C16H13Cl3N2OS/c17-12-1-2-13(14(18)7-12)15(8-21-5-4-20-10-21)22-9-11-3-6-23-16(11)19/h1-7,10,15H,8-9H2
IUPAC Name
1-{2-[(2-chlorothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
SMILES
ClC1=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=CS1

References

General References
  1. Electronic Medicines Compendium: Tioconazole 283 mg/ml medicated nail lacquer [Link]
Human Metabolome Database
HMDB0015142
KEGG Drug
D00890
KEGG Compound
C08082
PubChem Compound
5482
PubChem Substance
46508604
ChemSpider
5282
BindingDB
50370218
RxNav
38298
ChEBI
77898
ChEMBL
CHEMBL1200438
Therapeutic Targets Database
DAP001268
PharmGKB
PA164746156
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tioconazole
FDA label
Download (784 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentOnychomycosis of Fingernail1

Pharmacoeconomics

Manufacturers
  • Pfizer laboratories div pfizer inc
  • L perrigo co
  • Novartis consumer health inc
Packagers
  • Johnson & Johnson Healthcare
  • Novartis AG
  • Walgreen Co.
Dosage Forms
FormRouteStrength
SolutionVaginal
Cream; ointmentTopical; Vaginal
Cream; suppositoryTopical; Vaginal
OintmentVaginal6.5 %
SuppositoryVaginal300 mg / sup
SuppositoryVaginal
InsertVaginal
OintmentTopical6.5 g/100g
SolutionTopical1 g
LotionTopical1 %
LotionTopical2 %
LotionTopical
OintmentTopical
OintmentVaginal6.5 g/100g
OintmentTopical300 mg/1g
OintmentVaginal65 mg/1g
SolutionTopical28 %
PowderTopical1 %
SuppositoryVaginal300 mg
CreamTopical
SuppositoryRectal
CreamTopical1 g
CreamTopical1 %
CreamVaginal
EmulsionTopical
PowderTopical
SolutionTopical
SprayCutaneous
CreamTopical1 %w/w
CreamTopical
LotionTopical10 mg
CreamTopical1.0 g
CreamTopical10 mg / g
SolutionAuricular (otic)28 g
OintmentVaginal300 mg/1
Prices
Unit descriptionCostUnit
Monistat-Derm 2% Cream 28.35 gm Tube41.99USD tube
Monistat-Derm 2% Cream 15 gm Tube32.0USD tube
Monistat 1 combination pack16.81USD each
Monistat 1 6.5% ointment3.6USD g
Vagistat-1 6.5% ointment3.6USD g
Tioconazole 1 6.5% ointment1.75USD 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
logP4.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0165 mg/mLALOGPS
logP4.86ALOGPS
logP5.3Chemaxon
logS-4.4ALOGPS
pKa (Strongest Basic)6.48Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area27.05 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity94.53 m3·mol-1Chemaxon
Polarizability36.84 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.966
Blood Brain Barrier+0.9814
Caco-2 permeable+0.5812
P-glycoprotein substrateNon-substrate0.5819
P-glycoprotein inhibitor INon-inhibitor0.911
P-glycoprotein inhibitor IINon-inhibitor0.5295
Renal organic cation transporterInhibitor0.5164
CYP450 2C9 substrateNon-substrate0.8248
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.946
CYP450 2C9 inhibitorInhibitor0.8757
CYP450 2D6 inhibitorInhibitor0.9032
CYP450 2C19 inhibitorInhibitor0.926
CYP450 3A4 inhibitorInhibitor0.8406
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9934
Ames testNon AMES toxic0.8092
CarcinogenicityNon-carcinogens0.8543
BiodegradationNot ready biodegradable0.9869
Rat acute toxicity2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7187
hERG inhibition (predictor II)Inhibitor0.6506
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-MSsplash10-001i-9322000000-f6f11c3dd1abefdb5472
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0009000000-2827a77fbda828e7453e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0009000000-27b855fca59ed08acb85
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0903000000-30ef91f27453208dd584
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-2ed7f788cac071d871e4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-94a2a2533441e3179663
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-001i-0900000000-fa59d0317db7f93d6c2a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0019-1619000000-7bfbe2de2c4aa4e6cd39
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0009000000-645a2e1ecc9694b6358e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001r-4095000000-834eb967401d0e4e9a70
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kr-2009000000-918468ad34a3a86a80c5
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9260000000-9560e82c94ddca46be30
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01c0-6902000000-1d75673154c4920660e5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9100000000-d8fb41548cc390fe7684
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-168.6599669
predicted
DarkChem Lite v0.1.0
[M-H]-176.11626
predicted
DeepCCS 1.0 (2019)
[M+H]+168.5859669
predicted
DarkChem Lite v0.1.0
[M+H]+178.47426
predicted
DeepCCS 1.0 (2019)
[M+Na]+169.0479669
predicted
DarkChem Lite v0.1.0
[M+Na]+184.99736
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60674.965 Da
References
  1. Ballard SA, Lodola A, Tarbit MH: A comparative study of 1-substituted imidazole and 1,2,4-triazole antifungal compounds as inhibitors of testosterone hydroxylations catalysed by mouse hepatic microsomal cytochromes P-450. Biochem Pharmacol. 1988 Dec 15;37(24):4643-51. [Article]
  2. Fliri AF, Loging WT, Thadeio PF, Volkmann RA: Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6. Epub 2004 Dec 29. [Article]
  3. Bellamine A, Lepesheva GI, Waterman MR: Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J Lipid Res. 2004 Nov;45(11):2000-7. Epub 2004 Aug 16. [Article]
  4. Guinea J, Sanchez-Somolinos M, Cuevas O, Pelaez T, Bouza E: Fluconazole resistance mechanisms in Candida krusei: the contribution of efflux-pumps. Med Mycol. 2006 Sep;44(6):575-8. [Article]
  5. Chau AS, Chen G, McNicholas PM, Mann PA: Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae. Antimicrob Agents Chemother. 2006 Nov;50(11):3917-9. Epub 2006 Sep 11. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
CYP51A1
Uniprot ID
Q16850
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
56805.26 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. Fliri AF, Loging WT, Thadeio PF, Volkmann RA: Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6. Epub 2004 Dec 29. [Article]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Ayub M, Levell MJ: The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione. Biochem Pharmacol. 1990 Oct 1;40(7):1569-75. doi: 10.1016/0006-2952(90)90456-u. [Article]
  2. Ayub M, Levell MJ: Structure-activity relationships of the inhibition of human placental aromatase by imidazole drugs including ketoconazole. J Steroid Biochem. 1988 Jul;31(1):65-72. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Current data supporting this enzyme inhibition is limited to one in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [Article]
  2. Sweeney BP, Bromilow J: Liver enzyme induction and inhibition: implications for anaesthesia. Anaesthesia. 2006 Feb;61(2):159-77. doi: 10.1111/j.1365-2044.2005.04462.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 20:52