Identification

Name
Itraconazole
Accession Number
DB01167  (APRD00040)
Type
Small Molecule
Groups
Approved, Investigational
Description

One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis.

Structure
Thumb
Synonyms
  • Itraconazol
  • Itraconazolum
  • Oriconazole
External IDs
R 51,211 / R-51211 / R51211
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ItraconazoleSolution10 mg/1mLOralPatriot Pharmaceuticals, LLC1997-02-21Not applicableUs
ItraconazoleCapsule100 mg/1OralCarilion Materials Management2005-02-01Not applicableUs10147 1700 03 nlmimage10 e60e7363
ItraconazoleCapsule100 mg/1OralPatriot Pharmaceuticals2005-02-01Not applicableUs10147 170020180913 8702 14xqs3m
OnmelTablet200 mg/1OralMerz Pharmaceuticals2012-11-012016-12-01Us
OnmelTablet200 mg/1OralStiefel Laboratories, Inc.2011-12-012013-01-25Us
SporanoxCapsule100 mg/1OralPhysicians Total Care, Inc.2004-07-192005-10-31Us
SporanoxCapsule100 mgOralJanssen Pharmaceuticals1993-12-31Not applicableCanada
SporanoxCapsule100 mg/1OralJanssen Pharmaceuticals1992-09-11Not applicableUs
SporanoxCapsule100 mg/1OralPhysicians Total Care, Inc.1996-01-222011-06-30Us
SporanoxSolution10 mg/1mLOralJanssen Pharmaceuticals, Inc.1997-02-21Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ItraconazoleSolution10 mg/1mLOralAmneal Pharmaceuticals2014-04-30Not applicableUs
ItraconazoleCapsule100 mg/1OralMylan Pharmaceuticals2012-07-26Not applicableUs
ItraconazoleCapsule, coated pellets100 mg/1OralAscend Laboratories, LLC2017-06-12Not applicableUs
ItraconazoleCapsule100 mg/1OralAv Pak2018-03-23Not applicableUs
ItraconazoleCapsule100 mg/1OralAccord Healthcare Limited2017-05-30Not applicableUs
ItraconazoleCapsule100 mg/1OralEon Labs, Inc.2004-05-28Not applicableUs00185 0550 30 nlmimage10 433ba1dd
ItraconazoleCapsule100 mg/1OralAlembic Pharmaceuticals Inc.2016-12-16Not applicableUs
ItraconazoleCapsule100 mg/1OralCadila Pharnmaceuticals2018-03-06Not applicableUs
ItraconazoleCapsule, coated pellets100 mg/1OralNorth Star Rx Llc2017-09-01Not applicableUs
ItraconazoleCapsule100 mg/1OralPar Pharmaceutical2016-07-01Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SporanoxItraconazole (10 mg/1mL) + Sodium Chloride (900 mg/100mL)KitOrtho-McNeil-Janssen Pharmaceuticals, Inc.1999-03-302008-12-31Us
International/Other Brands
Itrizole / Oriconazole / Sporal / Sporanox
Categories
UNII
304NUG5GF4
CAS number
84625-61-6
Weight
Average: 705.633
Monoisotopic: 704.239307158
Chemical Formula
C35H38Cl2N8O4
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=CC=C(Cl)C=C2Cl)C=C1

Pharmacology

Indication

For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.

Associated Conditions
Pharmacodynamics

Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.

Mechanism of action

Itraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Human
ALanosterol 14-alpha demethylase
inhibitor
Yeast
Absorption

The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.

Volume of distribution
  • 796 ± 185 L
Protein binding

99.8%

Metabolism

Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.

Route of elimination

Itraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.

Half life

21 hours

Clearance
  • 381 +/- 95 mL/minute [IV administration]
Toxicity

No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.

Affected organisms
  • Fungi, yeast and protozoans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Itraconazole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Itraconazole.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Itraconazole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Itraconazole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Itraconazole.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Itraconazole.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Itraconazole.
AbemaciclibThe risk or severity of adverse effects can be increased when Itraconazole is combined with Abemaciclib.
AbexinostatThe risk or severity of QTc prolongation can be increased when Itraconazole is combined with Abexinostat.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Itraconazole.
Food Interactions
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Avoid taking with grapefruit juice.
  • Take after a full meal.
  • Take with food.

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
Not Available
External Links
Human Metabolome Database
HMDB0015298
KEGG Drug
D00350
PubChem Compound
55283
PubChem Substance
46505954
ChemSpider
49927
BindingDB
50127138
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
ATC Codes
J02AC02 — Itraconazole
AHFS Codes
  • 08:14.08 — Azoles
FDA label
Download (1.58 MB)
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentSkin Basal Cell Carcinoma1
0RecruitingBasic SciencePharmacokinetics1
0RecruitingOtherEsophageal Cancers1
0RecruitingTreatmentBasal Cell Carcinoma (BCC)1
0RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingBasic ScienceAdvanced Solid Tumors / Relapsed/Refractory Lymphoma1
1Active Not RecruitingOtherAdvanced (Inoperable) Non Small Cell Lung Cancer / Advanced Non Small Cell Lung Cancer1
1Active Not RecruitingOtherOncology, Medical1
1Active Not RecruitingTreatmentGlioblastomas1
1Active Not RecruitingTreatmentMetastatic Melanoma, BRAF V600 Mutation Positive1
1Active Not RecruitingTreatmentNeoplasms1
1Active Not RecruitingTreatmentNeoplasms Metastasis1
1Active Not RecruitingTreatmentOncology, Medical1
1CompletedNot AvailableCandidiasis infection / Dermatomycoses / Fungal infection of the dermal / Histoplasmosis1
1CompletedNot AvailableDrug-Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics1
1CompletedNot AvailableHealthy Participants / Healthy Volunteers1
1CompletedNot AvailableHealthy Volunteers4
1CompletedNot AvailableHealthy Volunteers / Hepatic Insufficiency / Renal Insufficiency,Chronic1
1CompletedNot AvailableOncology, Medical1
1CompletedNot AvailableTumors, Solid1
1CompletedBasic ScienceAlzheimer's Disease (AD) / Healthy Volunteers1
1CompletedBasic ScienceClinical Trials, Phase I as Topic1
1CompletedBasic ScienceDDI (Drug-Drug Interaction) / Healthy Volunteers / Pharmacokinetics1
1CompletedBasic ScienceHealthy Participants2
1CompletedBasic ScienceHealthy Volunteers11
1CompletedBasic ScienceHealthy Volunteers: Asian, Non-Asian1
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics of ASP37001
1CompletedBasic ScienceInflammatory Bowel Diseases (IBD)1
1CompletedBasic ScienceThrombosis2
1CompletedBasic ScienceTumors, Solid1
1CompletedOtherBiological Availability1
1CompletedOtherDrug Interaction Potentiation / Healthy Volunteers1
1CompletedOtherHealthy Participants2
1CompletedOtherHealthy Volunteers3
1CompletedOtherHealthy Volunteers / Non-Smokers1
1CompletedOtherMalignancies Multiple1
1CompletedTreatmentAdvanced Solid Tumors2
1CompletedTreatmentAsthma Bronchial1
1CompletedTreatmentBacterial Infections1
1CompletedTreatmentCachexia1
1CompletedTreatmentCystic Fibrosis (CF)1
1CompletedTreatmentDrug Drug Interaction (DDI)1
1CompletedTreatmentDrug Interactions2
1CompletedTreatmentHealthy Participants2
1CompletedTreatmentHealthy Patient Study1
1CompletedTreatmentHealthy Volunteers22
1CompletedTreatmentHistoplasmosis / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentJapanese Healthy Adult Males1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNocturia1
1CompletedTreatmentPain, Neuropathic1
1CompletedTreatmentPediatric, Cancer1
1CompletedTreatmentPharmacokinetic Study in Healthy Male Volunteers1
1CompletedTreatmentPharmacokinetics3
1CompletedTreatmentPulmonary Disease, Chronic Obstructive1
1CompletedTreatmentRelapsed Multiple Myeloma1
1CompletedTreatmentSinusitis1
1CompletedTreatmentSpinal Muscular Atrophy (SMA)1
1RecruitingBasic ScienceAutoimmune Diseases / Drug Drug Interactions / Fibrotic Disease1
1RecruitingBasic ScienceHealthy Volunteers2
1RecruitingOtherHealthy Volunteers2
1RecruitingTreatmentAdvanced Malignancies (Except Leukemia) / Advanced Malignancies Except Leukemia / Non-Small Cell Lung Cancer (ALK-positive) / Non-Small Cell Lung Cancer (c-Met Dependent) / Non-Small Cell Lung Cancer (ROS Marker Positive) / Non-Small Cell Lung Cancer ALK-positive / Non-Small Cell Lung Cancer c-Met Dependent / Non-Small Cell Lung Cancer ROS Marker Positive / Systemic Anaplastic Large-Cell Lymphoma1
1RecruitingTreatmentCytochrome P450 Interaction1
1TerminatedBasic SciencePolycystic Ovaries Syndrome1
1WithdrawnTreatmentAlzheimer's Disease (AD)1
1WithdrawnTreatmentHealthy Volunteers1
1, 2CompletedTreatmentBlastomycosis / Histoplasmosis / Sporotrichosis1
1, 2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1, 2RecruitingTreatmentPlatinum-resistant Epithelial Ovarian Cancer1
1, 2WithdrawnTreatmentCastration-Resistant Prostate Cancer (CRPC) / Prostate Cancer1
2Active Not RecruitingTreatmentAdenocarcinoma, Prostate / Prostate Cancer / Recurrent Prostate Carcinoma / Stage I Prostate Adenocarcinoma AJCC v7 / Stage II Prostate Adenocarcinoma AJCC v7 / Stage III Prostate Adenocarcinoma AJCC v71
2CompletedTreatmentAspergillosis / Lung Diseases, Fungal1
2CompletedTreatmentBasal Cell Carcinoma (BCC) / Skin Cancers1
2CompletedTreatmentCystic Fibrosis (CF) / Prophylaxis of Aspergillus infection1
2CompletedTreatmentHematological Diseases / Neutropenia, Febrile1
2CompletedTreatmentHistoplasmosis / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Meningitis, Cryptococcal1
2CompletedTreatmentMycoses1
2CompletedTreatmentOnychomycosis1
2CompletedTreatmentProstate Cancer1
2Not Yet RecruitingPreventionNeutropenias1
2Not Yet RecruitingTreatmentMycetoma1
2Not Yet RecruitingTreatmentTinea infections1
2RecruitingTreatmentLung Cancers1
2TerminatedTreatmentAndrogen-insensitive Prostate Cancer / Castrate-resistant Prostate Cancer (CRPC) / Hormone-Refractory Prostate Cancer / Metastatic Disease / Prostate Cancer / Prostatic Neoplasms1
2TerminatedTreatmentRecurrent Non Small Cell Lung Cancer1
2Unknown StatusPreventionAllogeneic Stem Cell Transplantation / Hematological Diseases1
2, 3CompletedTreatmentAspergillosis, Allergic Bronchopulmonary1
2, 3CompletedTreatmentMinor burns1
2, 3RecruitingTreatmentAspergillosis, Allergic Bronchopulmonary1
2, 3RecruitingTreatmentChronic Rhinosinusitis1
2, 3RecruitingTreatmentInfections, Fungal1
2, 3RecruitingTreatmentMinor burns1
3CompletedPreventionAntifungal Prophylaxis of Invasive Fungal Infections1
3CompletedPreventionFungaemia / Infections, Fungal1
3CompletedSupportive CareCancers1
3CompletedTreatmentBlastomycosis / Histoplasmosis / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentOnychomycosis / Onychomycosis, Toenail Onychomychosis, Toenail Fungus1
3Not Yet RecruitingTreatmentAntifungal Drugs in Onychomycosis1
3Not Yet RecruitingTreatmentChronic Pulmonary Aspergillosis1
3Not Yet RecruitingTreatmentOvarian Carcinoma / Signal Transduction Pathway Deregulation / Therapy-Associated Cancer1
4CompletedNot AvailableFevers / Neoplasms, Hematologic / Neutropenias1
4CompletedNot AvailableNeutropenias1
4CompletedBasic SciencePharmacodynamics / Pharmacokinetics1
4CompletedPreventionCystic Fibrosis (CF)1
4CompletedPreventionInvasive Fungal Infections1
4CompletedPreventionMycoses / Neoplasms, Brain / Neuroblastomas / Retinoblastoma / Wilms' tumor1
4CompletedTreatmentChronic Cavitary Pulmonary Aspergillosis1
4CompletedTreatmentNeoplasms, Hematologic1
4CompletedTreatmentOnychomycosis, Toe1
4CompletedTreatmentPulmonary Fungal Infection1
4Not Yet RecruitingBasic ScienceHealthy Volunteers1
4RecruitingNot AvailableNeutropenias / Systemic Mycosis1
4TerminatedPreventionGraft Versus Host Disease (GVHD)1
4TerminatedTreatmentAspergillosis, Allergic Bronchopulmonary / Cystic Fibrosis (CF)1
Not AvailableActive Not RecruitingNot AvailableSystemic Fungal Infections1
Not AvailableCompletedSupportive CareCancers1
Not AvailableCompletedTreatmentEsophageal Candidiasis / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHistoplasmosis / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Meningitis, Cryptococcal1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Oral Candidiasis2
Not AvailableCompletedTreatmentNeoplasms Metastasis / Neoplasms, Breast1
Not AvailableCompletedTreatmentVulvovaginal Candidiasis1
Not AvailableNot Yet RecruitingTreatmentSkin Basal Cell Carcinoma1

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, coated pelletsOral100 mg/1
SolutionOral10 mg/1mL
TabletOral200 mg/1
CapsuleOral100 mg
CapsuleOral100 mg/1
Kit
SolutionOral10 mg
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)
US5633015No1994-05-272014-05-27Us
CA2142848No1999-11-162013-08-27Canada
CA1336498No1995-08-012012-08-01Canada
US6407079No1999-06-182019-06-18Us
US6509038No1997-05-122017-05-12Us
US7081255No1997-05-122017-05-12Us
US8486456No2008-10-032028-10-03Us
US8591948No1997-05-122017-05-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)166.2 °CNot Available
water solubilityInsolubleNot Available
logP5.66HTTP://WWW.RXLIST.COM
pKa3.70Not Available
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
Polarizability74.71 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
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0329000000-18fc35342fd0b509b439
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0112100900-c45b863fbc00a8c449b4

Taxonomy

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
Phenylpiperazine / N-arylpiperazine / Phenyltriazole / Phenyl-1,2,4-triazole / Aminophenyl ether / Phenol ether / Phenoxy compound / Tertiary aliphatic/aromatic amine / 1,3-dichlorobenzene / Dialkylarylamine
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)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Cotrim PC, Garrity LK, Beverley SM: Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection. J Biol Chem. 1999 Dec 31;274(53):37723-30. [PubMed:10608831]
  3. Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, Quindos G: Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9. [PubMed:16964330]
Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
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 (By similarity).
Gene Name
ERG11
Uniprot ID
P50859
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
61304.95 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Gachotte D, Pierson CA, Lees ND, Barbuch R, Koegel C, Bard M: A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11173-8. [PubMed:9326581]
  4. Henry KW, Nickels JT, Edlind TD: Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother. 2000 Oct;44(10):2693-700. [PubMed:10991846]
  5. Morales IJ, Vohra PK, Puri V, Kottom TJ, Limper AH, Thomas CF Jr: Characterization of a lanosterol 14 alpha-demethylase from Pneumocystis carinii. Am J Respir Cell Mol Biol. 2003 Aug;29(2):232-8. Epub 2003 Feb 26. [PubMed:12606318]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  2. Flockhart Table - Indiana University [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  2. Flockhart Table - Indiana University [Link]
Details
3. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:16141567]
  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. [PubMed:15969931]
  3. 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]
  4. 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. [PubMed:10668858]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  6. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 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]
  2. Jung SM, Kim KA, Cho HK, Jung IG, Park PW, Byun WT, Park JY: Cytochrome P450 3A inhibitor itraconazole affects plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients. Clin Pharmacol Ther. 2005 Nov;78(5):520-8. doi: 10.1016/j.clpt.2005.07.007. Epub 2005 Sep 26. [PubMed:16321618]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:17101742]
Kind
Protein
Organism
Human
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. 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]
Kind
Protein
Organism
Human
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. 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]
  2. 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. [PubMed:9574817]

Transporters

Kind
Protein
Organism
Human
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. [PubMed:11716514]
  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. [PubMed:11751127]
  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. [PubMed:12699389]
  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. [PubMed:10746169]
  5. Masuda S, Inui K: [Molecular mechanisms on drug transporters in the drug absorption and disposition]. Nihon Rinsho. 2002 Jan;60(1):65-73. [PubMed:11808341]
  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. [PubMed:12621384]
  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. [PubMed:15969931]
  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. [PubMed:16041596]
  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. [PubMed:16084853]
Kind
Protein
Organism
Human
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. [PubMed:22541068]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:35