Itraconazole

Identification

Summary

Itraconazole is a triazole antifungal agent used to treat various fungal infections, such as blastomycosis and onychomycosis.

Brand Names
Sporanox, Tolsura
Generic Name
Itraconazole
DrugBank Accession Number
DB01167
Background

First synthesized in the early 1980s, itraconazole is a broad-spectrum triazole antifungal agent used to treat a variety of infections.1 It is a 1:1:1:1 racemic mixture of four diastereomers, made up of two enantiomeric pairs, each possessing three chiral centers.5 Itraconazole was first approved in the US in 1992 6 and is available orally. While the intravenous formulation of the drug was formerly available, it was discontinued in the US in 2007.4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 705.633
Monoisotopic: 704.239307158
Chemical Formula
C35H38Cl2N8O4
Synonyms
  • (±)-1-SEC-BUTYL-4-(P-(4-(P-(((2R*,4S*)-2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)-1-PIPERAZINYL)PHENYL)-.DELTA.(SUP 2)-1,2,4-TRIAZOLIN-5-ONE
  • 3H-1,2,4-TRIAZOL-3-ONE, 4-(4-(4-(4-((2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)-1-PIPERAZINYL)PHENYL)-2,4-DIHYDRO-2-(1-METHYLPROPYL)-
  • Itraconazol
  • Itraconazole
  • ITRACONAZOLE COMPONENT OF SUBA-ITRACONAZOLE
  • Itraconazolum
  • Oriconazole
External IDs
  • NSC-759239
  • R 51,211
  • R-51211
  • R51211

Pharmacology

Indication

Itraconazole is indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients:5,6

  • Blastomycosis, pulmonary and extrapulmonary
  • Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis, and
  • Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy

It is also indicated for the treatment of the following fungal infections in non-immunocompromised patients:5

  • Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium)
  • Onychomycosis of the fingernail due to dermatophytes (tinea unguium).

Itraconazole oral solution is indicated for the treatment of oropharyngeal and esophageal candidiasis.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAspergillosis••••••••••••
Treatment ofBlastomycosis••••••••••••
Treatment ofChromomycosis••••••••••••
Treatment ofCoccidioidal meningitis••• •••••
Treatment ofDermatomycoses••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Itraconazole is an antifungal agent that inhibits cell growth and promotes cell death of fungi.1 It exhibits in vitro activity against Blastomyces dermatitidis, Histoplasma capsulatum, Histoplasma duboisii, Aspergillus flavus, Aspergillus fumigatus, and Trichophyton species.5

Mechanism of action

Itraconazole mediates its antifungal activity by inhibiting 14α-demethylase, a fungal cytochrome P450 enzyme that converts lanosterol to ergosterol, a vital component of fungal cell membranes.5 The azole nitrogen atoms in the chemical structure of itraconazole form a complex with the active site, or the haem iron, of the fungal enzyme to impede its function.1,4 The accumulation of lanosterol and 14-methylated sterols results in increased permeability of the fungal cell membrane, and modified membrane-bound enzyme activity, and dysregulated chitin synthesis.1,2,3 Other proposed mechanisms of action of itraconazole include the inhibition of fungal cytochrome c oxidative and peroxidative enzymes that also lead to the disruption of fungal cell membranes.1

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Candida tropicalis
Absorption

Itraconazole is rapidly absorbed after oral administration. As oral capsules, peak plasma concentrations of itraconazole are reached within two to five hours. The observed absolute oral bioavailability of itraconazole is about 55%. Itraconazole exposure is lower with the capsule formulation than with the oral solution when the same dose of the drug is given.5 Maximal drug absorption is achieved under adequate gastric acidity.1,5

As a consequence of non-linear pharmacokinetics, itraconazole accumulates in plasma during multiple dosing. Steady-state concentrations are generally reached within about 15 days, with Cmax values of 0.5 μg/mL, 1.1 μg/mL and 2.0 μg/mL after oral administration of 100 mg once daily, 200 mg once daily and 200 mg b.i.d., respectively.5

Volume of distribution

The volume of distribution is more than 700 L in adults.4,5 Itraconazole is lipophilic and extensively distributed into tissues. Concentrations in the lung, kidney, liver, bone, stomach, spleen and muscle were found to be two to three times higher than corresponding concentrations in plasma, and the uptake into keratinous tissues, skin in particular, up to four times higher. Concentrations in the cerebrospinal fluid are much lower than in plasma.5

Protein binding

Most of the itraconazole in plasma is bound to protein (99.8%), with albumin being the main binding component (99.6% for the hydroxy-metabolite). It also has a marked affinity for lipids. Only 0.2% of the itraconazole in plasma is present as the free drug.5

Metabolism

Itraconazole is extensively metabolized in the liver. In vitro studies have shown that CYP3A4 is the major enzyme involved in the metabolism of itraconazole.5 While itraconazole can be metabolized to more than 30 metabolites,2 the main metabolite is hydroxyitraconazole. Hydroxyitraconazole has in vitro antifungal activity comparable to itraconazole; trough plasma concentrations of this metabolite are about twice those of the parent compound.5

Other metabolites include keto-itraconazole and N-dealkyl-itraconazole.4

Hover over products below to view reaction partners

Route of elimination

Itraconazole is excreted mainly as inactive metabolites in urine (35%) and in feces (54%) within one week of an oral solution dose. Renal excretion of itraconazole and the active metabolite hydroxyitraconazole account for less than 1% of an intravenous dose. Based on an oral radiolabeled dose, fecal excretion of unchanged drug ranges from 3% to 18% of the dose. As the re-distribution of itraconazole from keratinous tissues appears to be negligible, the elimination of itraconazole from these tissues is related to epidermal regeneration. Contrary to plasma, the concentration in skin persists for two to four weeks after discontinuation of a 4-week treatment and in nail keratin – where itraconazole can be detected as early as one week after the start of treatment – for at least six months after the end of a 3-month treatment period.5

Half-life

The terminal half-life of itraconazole generally ranges from 16 to 28 hours after a single dose and increases to 34 to 42 hours with repeated dosing.5 The metabolite of itraconazole is excreted from the plasma more rapidly than the parent compound.1

Clearance

The mean total plasma clearance following intravenous administration is 278 mL/min. Itraconazole clearance decreases at higher doses due to saturable hepatic metabolism.5

Adverse Effects
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Toxicity

In rats, the oral and intraperitoneal LD50 values were >320 mg/kg and 100 mg/kg, respectively.8

There is limited clinical information regarding itraconazole overdoses. Reported toxic trough levels are over 3 mcg/mL.1 Itraconazole is not removed by dialysis; thus, supportive measures should be initiated in the event of an overdose.5 There is no known antidote to itraconazole poisoning.1

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
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Itraconazole.
AbametapirThe serum concentration of Itraconazole can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Itraconazole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Itraconazole.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Itraconazole.
Food Interactions
  • Exercise caution with grapefruit products. While there is inconclusive evidence of the effect of grapefruit products on the systemic exposure to itraconazole, they may affect drug absorption.
  • Take with food. Food promotes maximal absorption of itraconazole.

Products

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Product Images
International/Other Brands
Itrizole / Oriconazole / Sporal
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ItraconazoleCapsule100 mg/1OralPatriot Pharmaceuticals2005-02-01Not applicableUS flag
ItraconazoleSolution10 mg/1mLOralPatriot Pharmaceuticals, LLC1997-02-21Not applicableUS flag
ItraconazoleCapsule100 mg/1OralCarilion Materials Management2005-02-01Not applicableUS flag
OnmelTablet200 mg/1OralStiefel Laboratories, Inc.2011-12-012013-01-25US flag
OnmelTablet200 mg/1OralMerz Pharmaceuticals, LLC2012-11-012020-11-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ItraconazoleCapsule100 mg/1OralTorrent Pharmaceuticals Limited2018-08-24Not applicableUS flag
ItraconazoleSolution10 mg/1mLOralAmneal Pharmaceuticals LLC2014-04-30Not applicableUS flag
ItraconazoleCapsule100 mg/1OralREMEDYREPACK INC.2022-10-21Not applicableUS flag
ItraconazoleSolution10 mg/1mLOralCamber Pharmaceuticals, Inc.2020-09-01Not applicableUS flag
ItraconazoleCapsule100 mg/1OralAvPAK2018-03-23Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ราเสทCapsule100 mgOralบริษัท ยูนีซัน จำกัด2007-02-13Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ALBISEC®Itraconazole (154.66 mg) + Secnidazole (166.66 mg)Capsule, coatedOral2006-11-102013-06-13Colombia flag
BIOPROX® TABLETA RECUBIERTAItraconazole (133.33 mg) + Secnidazole (666.667 mg)Tablet, coatedOralBIOCHEM FARMACEUTICA DE COLOMBIAS.A.2018-03-22Not applicableColombia flag
SporanoxItraconazole (10 mg/1mL) + Sodium chloride (900 mg/100mL)KitIntravenousOrtho-McNeil-Janssen Pharmaceuticals, Inc.1999-03-302008-12-31US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Ciclopirox 3% / Itraconazole 5% / Urea 20%Itraconazole (5 g/100g) + Ciclopirox olamine (3 g/100g) + Urea (20 g/100g)CreamTopicalSincerus Florida, LLC2019-05-20Not applicableUS flag
Fluconazole 4% / Ibuprofen 2% / Itraconazole 1% / Terbinafine HCl 4%Itraconazole (1 g/100g) + Fluconazole (4 g/100g) + Ibuprofen (2 g/100g) + Terbinafine (4 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag

Categories

ATC Codes
J02AC02 — Itraconazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Phenyl-1,2,4-triazoles / Aminophenyl ethers / Phenoxy compounds / Aniline and substituted anilines / Dichlorobenzenes / Dialkylarylamines / Alkyl aryl ethers / Ketals / Aryl chlorides
show 8 more
Substituents
1,2,4-triazole / 1,3-dichlorobenzene / Acetal / Alkyl aryl ether / Amine / Aminophenyl ether / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide
show 30 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
N-arylpiperazine, triazole antifungal drug, conazole antifungal drug, dioxolane, dichlorobenzene, triazoles, cyclic ketal (CHEBI:6076)
Affected organisms
  • Fungi, yeast and protozoans

Chemical Identifiers

UNII
304NUG5GF4
CAS number
84625-61-6
InChI Key
VHVPQPYKVGDNFY-ZPGVKDDISA-N
InChI
InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
IUPAC Name
1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
SMILES
CCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1

References

Synthesis Reference

Jong-Soo Woo, Hong-Gi Yi, "Antifungal oral composition containing itraconazole and process for preparing same." U.S. Patent US6039981, issued May, 1998.

US6039981
General References
  1. Pierard GE, Arrese JE, Pierard-Franchimont C: Itraconazole. Expert Opin Pharmacother. 2000 Jan;1(2):287-304. doi: 10.1517/14656566.1.2.287 . [Article]
  2. De Beule K, Van Gestel J: Pharmacology of itraconazole. Drugs. 2001;61 Suppl 1:27-37. doi: 10.2165/00003495-200161001-00003. [Article]
  3. Kurn H, Wadhwa R: Itraconazole. . [Article]
  4. Lestner J, Hope WW: Itraconazole: an update on pharmacology and clinical use for treatment of invasive and allergic fungal infections. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):911-26. doi: 10.1517/17425255.2013.794785. Epub 2013 May 6. [Article]
  5. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]
  6. FDA Approved Drug Products: TOLSURA (itraconazole) capsules, for oral use (December 2018) [Link]
  7. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Solution (February 2024) [Link]
  8. Cayman Chemical: Itraconazole MSDS [Link]
Human Metabolome Database
HMDB0015298
KEGG Drug
D00350
PubChem Compound
55283
PubChem Substance
46505954
ChemSpider
49927
BindingDB
50127138
RxNav
28031
ChEBI
6076
ChEMBL
CHEMBL22587
Therapeutic Targets Database
DAP000631
PharmGKB
PA450132
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Itraconazole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceFungal Infections1
4CompletedBasic SciencePharmacodynamics / Pharmacokinetics1
4CompletedOtherNeutropenia1
4CompletedPreventionBrain Neoplasm / Fungal Infections / Neuroblastoma (NB) / Retinoblastoma / Wilms' tumor1
4CompletedPreventionCystic Fibrosis (CF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • AQ Pharmaceuticals Inc.
  • Centocor Ortho Biotech Inc.
  • Eon Labs
  • Hospira Inc.
  • Janssen-Ortho Inc.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Patriot Pharmaceuticals
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
Dosage Forms
FormRouteStrength
Capsule, coatedOral
Tablet, coatedOral
CreamTopical
Capsule, coatedOral100 mg
SolutionTopical
SolutionOral1 g
CapsuleOral
Capsule, coated pelletsOral100 mg/1
SolutionOral10 mg/1mL
CapsuleOral50.000 mg
CapsuleOral50 MG
Capsule, coatedOral50 mg
TabletOral100 mg
CapsuleOral100.000 mg
TabletOral200 mg/1
CapsuleOral100.00 mg
CapsuleOral
Capsule, coatedOral200 mg
CapsuleOral100 MG
SolutionOral50 mg/5ml
CapsuleOral100 mg/1
Injection, solution, concentrateParenteral10 mg/mL
KitIntravenous
SolutionOral10 mg / mL
SolutionOral
SolutionOral10 mg/ml
SolutionIntravenous10 mg
Capsule, coated pelletsOral100 mg
Capsule, gelatin coatedOral65 mg/1
Prices
Unit descriptionCostUnit
Itraconazole 28 100 mg capsule Disp Pack270.89USD disp
Itraconazole powder32.13USD g
Sporanox 100 mg capsule12.14USD capsule
Itraconazole 100 mg capsule9.46USD capsule
Sporanox 10 mg/ml Solution1.41USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5633015No1997-05-272014-05-27US flag
CA2142848No1999-11-162013-08-27Canada flag
CA1336498No1995-08-012012-08-01Canada flag
US6407079No2002-06-182019-06-18US flag
US6509038No2003-01-212017-05-12US flag
US7081255No2006-07-252017-05-12US flag
US8486456No2013-07-162028-10-03US flag
US8591948No2013-11-262017-05-12US flag
US9713642No2017-07-252033-06-21US flag
US8771739No2014-07-082023-07-25US flag
US8921374No2014-12-302033-06-21US flag
US9272046No2016-03-012033-06-21US flag
US10463740No2019-11-052033-06-21US flag
US10806792No2020-10-202033-06-21US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)168-170https://www.fishersci.com/store/msds?partNumber=AC452870050&countryCode=US&language=en
logP5.66https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020083s068lbl.pdf
pKa3.7https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020083s068lbl.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.00964 mg/mLALOGPS
logP5.48ALOGPS
logP7.31Chemaxon
logS-4.9ALOGPS
pKa (Strongest Basic)3.91Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area100.79 Å2Chemaxon
Rotatable Bond Count11Chemaxon
Refractivity200.4 m3·mol-1Chemaxon
Polarizability74.5 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9973
Blood Brain Barrier-0.6151
Caco-2 permeable+0.5511
P-glycoprotein substrateSubstrate0.6397
P-glycoprotein inhibitor IInhibitor0.7973
P-glycoprotein inhibitor IINon-inhibitor0.88
Renal organic cation transporterNon-inhibitor0.7497
CYP450 2C9 substrateNon-substrate0.8116
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.7666
CYP450 2C9 inhibitorInhibitor0.618
CYP450 2D6 inhibitorNon-inhibitor0.8622
CYP450 2C19 inhibitorInhibitor0.5703
CYP450 3A4 inhibitorInhibitor0.5279
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8219
Ames testAMES toxic0.5303
CarcinogenicityNon-carcinogens0.7478
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3118 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5782
hERG inhibition (predictor II)Inhibitor0.6096
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0lz0-0594300000-f8fca354ab686af07f2d
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0lz0-0594300000-f8fca354ab686af07f2d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0329000000-18fc35342fd0b509b439
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0112100900-c45b863fbc00a8c449b4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000001900-39268622047a9d0d3ce6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0000009500-5e1c78e13d8316577ce6
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000008900-0bc31ec93cdd7fc8af91
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-5040059600-4331e6f93103450e5aea
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-06di-1023369300-510ac59142eabd07bc26
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f6x-2089038100-4d82756794f352778da3
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-306.3586824
predicted
DarkChem Lite v0.1.0
[M-H]-249.58968
predicted
DeepCCS 1.0 (2019)
[M+H]+309.3954824
predicted
DarkChem Lite v0.1.0
[M+H]+251.41457
predicted
DeepCCS 1.0 (2019)
[M+Na]+307.3565824
predicted
DarkChem Lite v0.1.0
[M+Na]+257.02042
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Candida tropicalis
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
This is a representative organ. Itraconazole works against various pathogenic fungi.
General Function
Sterol 14alpha-demethylase that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions (By similarity). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (By similarity). In filamentous fungi, during the initial step of this module, lanosterol (lanosta-8,24-dien-3beta-ol) can be metabolized to eburicol (By similarity). Sterol 14alpha-demethylase catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of both these sterols in the form of formate, and converts eburicol and lanosterol to 14-demethyleburicol (4,4,24-trimethylergosta-8,14,24(28)-trienol) and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, respectively, which are further metabolized by other enzymes in the pathway to ergosterol (By similarity). Can also use substrates not intrinsic to fungi, such as 24,25-dihydrolanosterol (DHL), producing 4,4-dimethyl-8,14-cholestadien-3-beta-ol, but at lower rates than the endogenous substrates (By similarity).
Specific Function
Heme binding
Gene Name
ERG11
Uniprot ID
P14263
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60927.455 Da
References
  1. Kurn H, Wadhwa R: Itraconazole. . [Article]
  2. Pierard GE, Arrese JE, Pierard-Franchimont C: Itraconazole. Expert Opin Pharmacother. 2000 Jan;1(2):287-304. doi: 10.1517/14656566.1.2.287 . [Article]
  3. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Niwa T, Shiraga T, Takagi A: Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005 Sep;28(9):1805-8. [Article]
  2. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [Article]
  3. Dresser GK, Spence JD, Bailey DG: Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000 Jan;38(1):41-57. [Article]
  4. Klotz U: Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist. Arzneimittelforschung. 2002;52(3):155-61. doi: 10.1055/s-0031-1299873. [Article]
  5. Zhang S, Jin S, Griffin C, Feng Z, Lin J, Venkatakrishnan K, Gupta N: Effects of Itraconazole and Rifampin on the Pharmacokinetics of Mobocertinib (TAK-788), an Oral Epidermal Growth Factor Receptor Inhibitor, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1044-1053. doi: 10.1002/cpdd.967. Epub 2021 Jun 19. [Article]
  6. Flockhart Table of Drug Interactions [Link]
  7. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  8. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxygen binding
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
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxygen binding
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
No
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...

Components:
References
  1. Zhang S, Jin S, Griffin C, Feng Z, Lin J, Venkatakrishnan K, Gupta N: Effects of Itraconazole and Rifampin on the Pharmacokinetics of Mobocertinib (TAK-788), an Oral Epidermal Growth Factor Receptor Inhibitor, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1044-1053. doi: 10.1002/cpdd.967. Epub 2021 Jun 19. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid 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
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Korashy HM, Shayeganpour A, Brocks DR, El-Kadi AO: Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci. 2007 May;97(1):32-43. Epub 2007 Feb 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. doi: 10.1080/004982598239579 . [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [Article]
  2. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW: Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002 Jan;46(1):160-5. [Article]
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
  4. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [Article]
  5. Masuda S, Inui K: [Molecular mechanisms on drug transporters in the drug absorption and disposition]. Nihon Rinsho. 2002 Jan;60(1):65-73. [Article]
  6. Lilja JJ, Backman JT, Laitila J, Luurila H, Neuvonen PJ: Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther. 2003 Mar;73(3):192-8. [Article]
  7. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [Article]
  8. Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R: Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK). Eur J Clin Pharmacol. 2005 Aug;61(7):531-6. Epub 2005 Jul 23. [Article]
  9. Shon JH, Yoon YR, Hong WS, Nguyen PM, Lee SS, Choi YG, Cha IJ, Shin JG: Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin Pharmacol Ther. 2005 Aug;78(2):191-201. [Article]
  10. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  11. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: SPORANOX (itraconazole) Oral Capsules (February 2024) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 27, 2024 23:09