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Identification
Name Fluconazole
Accession Number DB00196 (APRD00327)
Type small molecule
Groups approved
Description

Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Biocanol
  • Biozolene
  • Diflucan
  • Elazor
  • Flucazol
  • Flucostat
  • Flukezol
  • Flunizol
  • Flusol
  • Pritenzol
  • Triflucan
Brand name mixtures Not Available
Categories
  • Antifungals
  • Antifungal Agents
CAS number 86386-73-4
Weight Average: 306.2708
Monoisotopic: 306.104065446
Chemical Formula C13H12F2N6O
InChI Key InChIKey=RFHAOTPXVQNOHP-UHFFFAOYSA-N
InChI
InChI=1S/C13H12F2N6O/c14-10-1-2-11(12(15)3-10)13(22,4-20-8-16-6-18-20)5-21-9-17-7-19-21/h1-3,6-9,22H,4-5H2
Plain Text
IUPAC Name
2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol
SMILES
OC(CN1C=NC=N1)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Cumenes and Derivatives
  • Phenethylamines
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Triazoles
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Alcohols and Polyols
  • Halobenzenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
  • Aryl Halides
Pharmacology
Indication For the treatment of fungal infections.
Pharmacodynamics Fluconazole, a synthetic antifungal agent of the imidazole class, is used to treat vaginal candidiasis. It inhibits the fungal lanosterol 14 alpha-demethylase which thereby prevents the formation of ergosterol which is an essential component in the fungal cell membrane.
Mechanism of action Fluconazole 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. Fluconazole 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.
Absorption 90%
Volume of distribution Not Available
Protein binding 11 to 12%
Metabolism

Hepatic
Route of elimination In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug.
Half life 30 hours (range 20-50 hours)
Clearance
  • 0.23 mL/min/Kg [adults]
  • 0.18 mL/min/Kg [In premature newborns within 36 hours of birth]
  • 0.22 mL/min/Kg [In premature newborns 6 days old]
  • 0.33 mL/min/Kg [In premature newborns 12 days old]
  • 0.4 mL/min/kg [9 Months-13 yearsreceiving single-oral 2 mg/kg]
  • 0.51 mL/min/Kg [9 Months-13 yearsreceiving single-oral 8 mg/kg]
  • 0.49 mL/min/Kg [5-15 yearsreceiving multiple IV 2 mg/kg]
  • 0.59 mL/min/Kg [5-15 yearsreceiving multiple IV 4 mg/kg]
  • 0.66 mL/min/Kg [5-15 yearsreceiving multiple IV 8 mg/kg]
Toxicity Symptoms of overdose include hallucinations and paranoid behavior.
Affected organisms
  • Fungi
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pfizer chemicals div pfizer inc
  • Aurobindo pharma usa inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Taro pharmaceutical industries ltd
  • Pfizer inc
  • Acs dobfar info sa
  • Apotex inc richmond hill
  • Hospira inc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Claris lifesciences ltd
  • Hikma farmaceutica portugal lda
  • Teva parenteral medicines inc
  • Baxter healthcare corp
  • Bedford laboratories
  • Pfizer central research
  • Apotex inc
  • Aurobindo pharma ltd
  • Dr reddys laboratories inc
  • Gedeon richter usa inc
  • Genpharm inc
  • Glenmark generics ltd
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Unique pharmaceutical laboratories
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Intravenous
Powder, for solution Oral
Solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Diflucan 40 mg/ml Suspension 35ml Bottle 203.65 USD bottle
Fluconazole 40 mg/ml Suspension 35ml Bottle 135.99 USD bottle
Diflucan 10 mg/ml Suspension 35ml Bottle 56.06 USD bottle
Fluconazole 10 mg/ml Suspension 35ml Bottle 35.94 USD bottle
Diflucan 150 mg tablet 24.71 USD tablet
Diflucan 200 mg tablet 20.82 USD tablet
Diflucan 150 mg Capsule 16.44 USD capsule
Fluconazole 200 mg tablet 14.26 USD tablet
Fluconazole powder 14.08 USD g
Fluconazole 150 mg tablet 13.93 USD tablet
Diflucan 100 mg tablet 12.61 USD tablet
Apo-Fluconazole-150 150 mg Capsule 9.18 USD capsule
Co Fluconazole 150 mg Capsule 9.18 USD capsule
Mylan-Fluconazole 150 mg Capsule 9.18 USD capsule
Pms-Fluconazole 150 mg Capsule 9.18 USD capsule
Fluconazole 100 mg tablet 8.95 USD tablet
Diflucan 50 mg tablet 8.05 USD tablet
Apo-Fluconazole 100 mg Tablet 5.81 USD tablet
Mylan-Fluconazole 100 mg Tablet 5.81 USD tablet
Fluconazole 50 mg tablet 5.7 USD tablet
Co Fluconazole 100 mg Tablet 5.42 USD tablet
Novo-Fluconazole 100 mg Tablet 5.42 USD tablet
Pms-Fluconazole 100 mg Tablet 5.42 USD tablet
Apo-Fluconazole 50 mg Tablet 3.28 USD tablet
Mylan-Fluconazole 50 mg Tablet 3.28 USD tablet
Co Fluconazole 50 mg Tablet 3.06 USD tablet
Novo-Fluconazole 50 mg Tablet 3.06 USD tablet
Pms-Fluconazole 50 mg Tablet 3.06 USD tablet
Diflucan-dextr 200 mg/100 ml 1.28 USD ml
Diflucan-saline 200 mg/100 ml 1.28 USD ml
Diflucan 2 mg/ml 0.6 USD ml
Fluconazole 2 mg/ml 0.33 USD ml
Fluconazole Omega 2 mg/ml 0.33 USD ml
Fluconazole-dext 200 mg/100 ml 0.32 USD ml
Fluconazole-ns 200 mg/100 ml 0.19 USD ml
Patents Not Available
Properties
State solid
Melting point 138 - 140 oC
Experimental Properties
Property Value Source
water solubility 1 mg/L PhysProp
logP 0.4 PhysProp
Predicted Properties
Property Value Source
water solubility 1.39e+00 g/l ALOGPS
logP 0.58 ALOGPS
logP 0.56 ChemAxon Molconvert
logS -2.34 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 81.65 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 97.20 ChemAxon Molconvert
polarizability 26.52 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00322 Link_out
PubChem Compound 3365 Link_out
PubChem Substance 46505735 Link_out
ChemSpider 3248 Link_out
BindingDB 25817 Link_out
ChEBI 46081 Link_out
ChEMBL 46081 Link_out
Therapeutic Targets Database DAP000628 Link_out
PharmGKB PA449653 Link_out
HET TPF Link_out
Drug Product Database 2245697 Link_out
RxList http://www.rxlist.com/cgi/generic/flucon.htm Link_out
Drugs.com http://www.drugs.com/cdi/fluconazole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fluconazole Link_out
ATC Codes
  • D01AC15
  • J02AC01
AHFS Codes
  • 08:14.08
PDB Entries Not Available
FDA label show (16.9 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Cytochrome P450 51

Pharmacological action: yes
Actions: inhibitor

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

Organism class: fungal
UniProt ID: P10613 Link_out
Gene: ERG11
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bellamine A, Lepesheva GI, Waterman MR: Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J Lipid Res. 2004 Nov;45(11):2000-7. Epub 2004 Aug 16. Pubmed
  2. Guinea J, Sanchez-Somolinos M, Cuevas O, Pelaez T, Bouza E: Fluconazole resistance mechanisms in Candida krusei: the contribution of efflux-pumps. Med Mycol. 2006 Sep;44(6):575-8. Pubmed
  3. Chau AS, Chen G, McNicholas PM, Mann PA: Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae. Antimicrob Agents Chemother. 2006 Nov;50(11):3917-9. Epub 2006 Sep 11. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Kunze KL, Wienkers LC, Thummel KE, Trager WF: Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab Dispos. 1996 Apr;24(4):414-21. Pubmed
  3. 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
  4. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  5. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Kunze KL, Wienkers LC, Thummel KE, Trager WF: Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab Dispos. 1996 Apr;24(4):414-21. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. 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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A5

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. Cytochrome P450 3A7

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

6. Cytochrome P450 11B1, mitochondrial

Actions: inhibitor

Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB

UniProt ID: P15538 Link_out
Gene: CYP11B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. Pubmed
  3. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.