Identification

Name
Itraconazole
Accession Number
DB01167
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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 705.633
Monoisotopic: 704.239307158
Chemical Formula
C35H38Cl2N8O4
Synonyms
  • Itraconazol
  • Itraconazole
  • Itraconazolum
  • Oriconazole
External IDs
  • R 51,211
  • R-51211
  • R51211

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
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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
Humans
ALanosterol 14-alpha demethylase
inhibitor
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.

Hover over products below to view reaction partners

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]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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
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
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.
AcebutololThe risk or severity of QTc prolongation can be increased when Itraconazole is combined with Acebutolol.
AceclofenacThe risk or severity of hyperkalemia can be increased when Itraconazole is combined with Aceclofenac.
AcemetacinThe risk or severity of hyperkalemia can be increased when Itraconazole is combined with Acemetacin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Itraconazole.
AcetaminophenItraconazole may increase the hepatotoxic activities of Acetaminophen.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Itraconazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products.
  • Avoid multivalent ions. Calcium, iron, and aluminum containing products taken up to 2 hours before and 6 hours after administration can decrease drug concentrations.
  • Take with food.

Products

Product Images
International/Other Brands
Itrizole / Oriconazole / Sporal
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ItraconazoleSolution10 mg/1mLOralPatriot Pharmaceuticals, LLC1997-02-21Not applicableUS flag
ItraconazoleCapsule100 mg/1OralCarilion Materials Management2005-02-01Not applicableUS flag10147 1700 03 nlmimage10 e60e7363
ItraconazoleCapsule100 mg/1OralPatriot Pharmaceuticals2005-02-01Not applicableUS flag10147 170020180913 8702 14xqs3m
OnmelTablet200 mg/1OralStiefel Laboratories, Inc.2011-12-012013-01-25US flag
OnmelTablet200 mg/1OralMerz Pharmaceuticals, LLC2012-11-012020-11-30US flag
SporanoxCapsule100 mg/1OralPhysicians Total Care, Inc.2004-07-192005-10-31US flag
SporanoxCapsule100 mg/1OralJanssen Pharmaceuticals, Inc.1992-09-11Not applicableUS flag
SporanoxCapsuleOralJanssen Pharmaceuticals1993-12-31Not applicableCanada flag
SporanoxSolution10 mg/1mLOralJanssen Pharmaceuticals, Inc.1997-02-21Not applicableUS flag
SporanoxCapsule100 mg/1OralPhysicians Total Care, Inc.1996-01-222011-06-30US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ItraconazoleCapsule100 mg/1OralAccord Healthcare Inc.2017-05-30Not applicableUS flag
ItraconazoleCapsule, coated pellets100 mg/1OralNorthstar RxLLC2017-09-01Not applicableUS flag
ItraconazoleSolution10 mg/1mLOralCamber Pharmaceuticals, Inc.2020-09-01Not applicableUS flag
ItraconazoleCapsule100 mg/1OralZydus Pharmaceuticals (USA) Inc.2018-03-06Not applicableUS flag
ItraconazoleCapsule100 mg/1OralAlembic Pharmaceuticals Limited2016-12-16Not applicableUS flag
ItraconazoleCapsule100 mg/1OralAlembic Pharmaceuticals Inc.2016-12-16Not applicableUS flag
ItraconazoleCapsule100 mg/1OralVensun Pharmaceuticals, Inc.2020-01-31Not applicableUS flag
ItraconazoleCapsule100 mg/1OralJubilant Cadista Pharmaceuticals Inc.2017-02-23Not applicableUS flag
ItraconazoleCapsule100 mg/1OralAmerican Health Packaging2017-04-07Not applicableUS flag
ItraconazoleCapsule100 mg/1OralAvPAK2018-03-23Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
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)

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[[email protected]]2CO[[email protected]@](CN3C=NC=N3)(O2)C2=CC=C(Cl)C=C2Cl)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
Not Available
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
AHFS Codes
  • 08:14.08 — Azoles
FDA label
Download (1.58 MB)
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic SciencePharmacodynamics / Pharmacokinetics1
4CompletedOtherNeutropenia1
4CompletedPreventionCystic Fibrosis (CF)1
4CompletedPreventionInvasive Fungal Infections1
4CompletedPreventionMycoses / Neoplasms, Brain / Neuroblastomas / Retinoblastoma / Wilms' tumor1
4CompletedTreatmentChronic Cavitary Pulmonary Aspergillosis1
4CompletedTreatmentOnychomycosis, Toe1
4CompletedTreatmentPulmonary Fungal Infection1
4RecruitingBasic ScienceInfections, Fungal1
4TerminatedPreventionGraft Versus Host Disease (GVHD)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, coatedOral154.66 mg
Tablet, coatedOral133.33 mg
CreamTopical
Capsule, coatedOral100 mg
SolutionTopical
SolutionOral1 g
Capsule100 mg
CapsuleOral100 MG
Capsule, coated pelletsOral100 mg/1
SolutionOral10 mg/1mL
SolutionOral
CapsuleOral50 MG
Capsule, coatedOral50 mg
Capsule, coated pellets100 mg
TabletOral200 mg/1
Capsule
Solution / dropsOral10 mg/1mL
CapsuleOral100 mg/1
KitIntravenous
SolutionOral10 mg/ml
CapsuleOral
Capsule, coatedOral33.33 mg
Capsule, gelatin coatedOral65 mg/1
SolutionOral150 ML
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
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

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

Targets

Kind
Protein
Organism
Humans
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
Not Available
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
Humans
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. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
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. Flockhart Table of Drug Interactions [Link]
Details
3. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
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. 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]
  4. Flockhart Table of Drug Interactions [Link]
  5. Link [Link]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
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
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. 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. [PubMed:17283379]
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. 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 . [PubMed:9574817]

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. [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]
  10. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [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. [PubMed:22541068]

Drug created on June 13, 2005 07:24 / Updated on October 27, 2020 11:12

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