NAV

Voriconazole

Identification

Summary

Voriconazoleis a triazole compound used to treat fungal infections.

Brand Names
Vfend
Generic Name
Voriconazole
DrugBank Accession Number
DB00582
Background

Voriconazole (Vfend, Pfizer) is a triazole antifungal medication used to treat serious fungal infections.14It is used to treat invasive fungal infections that are generally seen in patients who are immunocompromised. These include invasive candidiasis, invasive aspergillosis, and emerging fungal infections. The increased affinity of voriconazole for 14-alpha sterol demethylase makes it useful against somefluconazole-resistant organisms.11

Voriconazole was approved by the FDA under the trade name Vfend on May 24, 2002.15

Type
Small Molecule
Groups
Approved
Structure
 3D
Similar Structures
Weight
Average: 349.3105
Monoisotopic: 349.11504471
Chemical Formula
C16H14F3N5O
Synonyms
  • (R-(R*,S*))-alpha-(2,4-difluorophenyl)-5-fluoro-beta-methyl-alpha-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol
  • (αR,βS)-α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol
  • VCZ
  • Voriconazol
  • Voriconazole
  • Voriconazolum
External IDs
  • DRG-0301
  • UK-109,496
  • UK-109496

Pharmacology

Indication

治疗esophageal candidiasis, cadidemia, invasive pulmonary aspergillosis, and serious fungal infections caused byScedosporium apiospermumandFusariumspp.13,14

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth.13It is known to cause hepatotoxic and photosensitivity reactions in some patients.

Mechanism of action

Voriconazole is used to treat fungal infections caused by a variety of organisms but includingAspergillus spp.andCandida spp. Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens.11,10,13Like other triazoles, voriconazole binds to 14-alpha sterol demethylase, also known as CYP51, and inhibits the demethylation of lanosterol as part of the ergosterol synthesis pathway in yeast and other fungi. The lack of sufficient ergosterol disrupts fungal cell membrane function and limits fungal cell growth. With fungal growth limited, the host's immune system is able to clear the invading organism.

Target Actions Organism
ACytochrome P450 51
antagonist
inhibitor
 Yeast
Absorption

The oral bioavailability is estimated to be 96% in healthy adults13. Population pharmacokinetic studies report a reduced bioavailability pediatric patients with a mean of 61.8% (range 44.6–64.5%) thought to be due to differences in first-pass metabolism or due to differences in diet6. Of note, transplant patients also have reduced bioavailability but this is known to increase with time after transplantation and may be due in part to gastrointestinal upset from surgery and some transplant medications. Tmax is 1-2 hours with oral administration. When administered with a high-fat meal Cmax decreases by 34% and AUC by 24%. pH does not have an effect on absorption of voriconazole. Differences in Cmax and AUC have been observed between healthy adult males and females with Cmax increasing by 83% and AUC by 113% although this has not been observed to significantly impact medication safety profiles.

Volume of distribution

The estimated volume of distribution of voriconazole is 4.6 L/kg13. Population pharmacokinetic studies estimate the median volume of distribution to be 77.6 L with the central compartment estimated at 1.07 L/kg6Voriconazole is known to achieve therapeutic concentrations in many tissues including the brain, lungs, liver, spleen, kidneys, and heart.

Protein binding

Voriconazole is 58% bound to plasma proteins13.

Metabolism

Voriconazole undergoes extensive hepatic metabolism through cytochrome enzymes CYP2C9, CYP2C19, and CYP3A4. CYP2C19 mediates N-oxidation with an apparent Km of 14 μM and an apparent Vmax of 0.22 nmol/min/nmol CYP2C19.8Voriconazole N-oxide is the major circulating metabolite, accounting for 72% of radiolabeled metabolites found.13CYP3A4 contributes to N-oxidation with a Km of 16 μM and Vmax of 0.05 nmol/min/nmol CYP3A4 as well as 4-hydroxylation with a Km of 11 μM and a Vmax of 0.10 nmol/min/nmol CYP3A4.8CYP3A5 and CYP3A7 provide minor contributions to N-oxidation and 4-hydroxylation. The N-oxide and 4-hydroxylated metabolites undergo glucuronidation and are excreted through the urine with other minor glucuronidated metabolites.9

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Route of elimination

伏立康唑是消除通过hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.13

Half-life

Voriconazole follows non-linear kinetics and has a terminal half-life of elimination which is dose-dependent.13

Clearance

The clearance of voriconazole is estimated to be a mean of 5.25-7 L/h in healthy adults for the linear portion of the drug's kinetics.6,7

Adverse Effects
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Toxicity

Symptoms of overdose include photophobia and possible QTc prolongation.13,14In case of overdose, supportive care and ECG monitoring are recommended. Activated charcoal may aid in the removal of unabsorbed drug. Voriconazole is cleared by hemodialysis at a rate of 121 mL/min which may be helpful in removing absorbed drug. Carcinogenicity studies found hepatocellular adenomas in female rats at doses of 50 mg/kg and hepatocellular carcinomas found in male rats at doses of 6 and 50 mg/kg. These doses are equivalent to 0.2 and 1.6 times the recommended maintenance dose (RMD). Studies in mice detected hepatocellular carcinomas in males at doses of 100 mg/kg or 1.4 times the RMD. Hepatocellular adenomas were detected in both male and female mice.

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details
Cytochrome P450 2C19 CYPC19*17 (T;T)/(C;T) C > T EffectDirectly Studied Patients with this genotype in CYP2C19 are ultra fast metabolizers and require higer doses of voriconazole to attain the therapeutic effect. Details
Cytochrome P450 2C19 CYP2C19*2 Not Available 681G>A Directly StudiedEffect The presence of this polymorphism in CYP2C19 is associated with poor metabolism of voriconazole. Details
Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A Directly StudiedEffect The presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of voriconazole. Details
Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C/991A>G ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T/991A>G…show all ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details
Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G ADRInferred Poor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders Details

Interactions

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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.
Drug Interaction
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1,2-Benzodiazepine The serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Voriconazole.
Abametapir The serum concentration of Voriconazole can be increased when it is combined with Abametapir.
Abatacept The metabolism of Voriconazole can be increased when combined with Abatacept.
Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Voriconazole.
Abiraterone The metabolism of Abiraterone can be decreased when combined with Voriconazole.
Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Voriconazole.
Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Voriconazole.
Aceclofenac The serum concentration of Aceclofenac can be increased when it is combined with Voriconazole.
Acemetacin 的血清浓度Acemetacin可以分辨ased when it is combined with Voriconazole.
Acenocoumarol Voriconazole may increase the anticoagulant activities of Acenocoumarol.
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Food Interactions
  • Take separate from meals. Take voriconazole at least one hour before or after eating for optimal absorption.

Products

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Product Images
Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Vfend Tablet, film coated 50 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU flag
Vfend Tablet, film coated 200 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU flag
Vfend Tablet, film coated 50 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Vfend Tablet, film coated 200 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Vfend Injection, powder, for solution 200 mg Intravenous Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Vfend Tablet 200 mg Oral Pfizer Canada Ulc 2004-11-12 Not applicable Canada flag
Vfend Tablet, film coated 50 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Vfend Tablet, film coated 200 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Vfend Tablet, film coated 50 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU flag
Vfend Tablet, film coated 50 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU flag
Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Ach-voriconazole Tablet 50 mg Oral Accord Healthcare Inc Not applicable Not applicable Canada flag
Ach-voriconazole Tablet 200 mg Oral Accord Healthcare Inc Not applicable Not applicable Canada flag
Apo-voriconazole Tablet 200 mg Oral Apotex Corporation 2014-04-14 Not applicable Canada flag
Apo-voriconazole Tablet 50 mg Oral Apotex Corporation 2014-04-14 Not applicable Canada flag
Auro-voriconazole Tablet 200 mg Oral Auro Pharma Inc Not applicable Not applicable Canada flag
Auro-voriconazole Tablet 50 mg Oral Auro Pharma Inc Not applicable Not applicable Canada flag
Jamp Voriconazole Tablet 50 mg Oral Jamp Pharma Corporation 2022-09-12 Not applicable Canada flag
Jamp Voriconazole Tablet 200 mg Oral Jamp Pharma Corporation 2022-09-12 Not applicable Canada flag
Med-voriconazole Tablet 200 mg Oral Generic Medical Partners Inc Not applicable Not applicable Canada flag
Mylan-voriconazole Tablet 200 mg Oral Mylan Pharmaceuticals Not applicable Not applicable Canada flag

Categories

ATC Codes
J02AC03 — Voriconazole
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Halopyrimidines/Fluorobenzenes/Aryl fluorides/Triazoles/Tertiary alcohols/Heteroaromatic compounds/Azacyclic compounds/Organopnictogen compounds/Organonitrogen compounds/Organofluorides
show 2 more
Substituents
1,2,4-triazole/Alcohol/Aromatic alcohol/Aromatic heteromonocyclic compound/Aryl fluoride/Aryl halide/Azacycle/Azole/Fluorobenzene/Halobenzene
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary alcohol, triazole antifungal drug, conazole antifungal drug, pyrimidines, difluorobenzene (CHEBI:10023)
Affected organisms
  • Yeast and other fungi

Chemical Identifiers

UNII
JFU09I87TR
CAS number
137234-62-9
InChI Key
BCEHBSKCWLPMDN-MGPLVRAMSA-N
InChI
InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16+/m0/s1
IUPAC Name
(3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
SMILES
C[C@@H](C1=NC=NC=C1F)[C@](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1

References

Synthesis Reference

Venkataraman Sundaram, Venkata Bhaskara Rao Uppala, Surya Prabhakar Akundi, Venkateswarlu Muvva, Vijayawardhan Chitta, Alekhya Donthula, Manoj Ramesh Kharkar, Surya Narayana Devarakonda, Subba Reddy Peddireddy, "Process For Preparing Voriconazole." U.S. Patent US20080194820, issued August 14, 2008.

 US20080194820
一般引用
  1. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8;347(6):408-15. [Article]
  2. Patterson TF, Boucher HW, Herbrecht R, Denning DW, Lortholary O, Ribaud P, Rubin RH, Wingard JR, DePauw B, Schlamm HT, Troke P, Bennett JE: Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin Infect Dis. 2005 Nov 15;41(10):1448-52. Epub 2005 Oct 13. [Article]
  3. Kullberg BJ, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Rex JH, Cleary JD, Rubinstein E, Church LW, Brown JM, Schlamm HT, Oborska IT, Hilton F, Hodges MR: Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005 Oct 22-28;366(9495):1435-42. [Article]
  4. Ally R, Schurmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, Hodges M, Troke P, Romero AJ: A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 2001 Nov 1;33(9):1447-54. Epub 2001 Sep 26. [Article]
  5. Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J: Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. [Article]
  6. Shi C, Xiao Y, Mao Y, Wu J, Lin N: Voriconazole: A Review of Population Pharmacokinetic Analyses. Clin Pharmacokinet. 2019 Jun;58(6):687-703. doi: 10.1007/s40262-019-00735-7. [Article]
  7. Bellmann R, Smuszkiewicz P: Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection. 2017 Dec;45(6):737-779. doi: 10.1007/s15010-017-1042-z. Epub 2017 Jul 12. [Article]
  8. Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H: Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6. doi: 10.1016/j.bcp.2007.03.012. Epub 2007 Mar 19. [Article]
  9. Roffey SJ, Cole S, Comby P, Gibson D, Jezequel SG, Nedderman AN, Smith DA, Walker DK, Wood N: The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab Dispos. 2003 Jun;31(6):731-41. [Article]
  10. Sanati H, Belanger P, Fratti R, Ghannoum M: A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. Antimicrob Agents Chemother. 1997 Nov;41(11):2492-6. doi: 10.1128/AAC.41.11.2492. [Article]
  11. Sabo是的,任SM:伏立康唑:一个新的恐怖主义风险保险法案zole antifungal. Ann Pharmacother. 2000 Sep;34(9):1032-43. doi: 10.1345/aph.19237. [Article]
  12. International Patent WO 98/58677: Pharmaceutical formulations containing voriconazole [Link]
  13. VFENDⓇ FDA Label [Link]
  14. Health Canada Approved Products: Vfend (voriconazole) multiple forms/routes [Link]
  15. VFend FDA Approval Letter [Link]
  16. FDA Approved Drug Products: VORICONAZOLE for injection, for intravenous use [Link]
  17. EMA Approved Products: Vfend (voriconazole) oral tablets [Link]
  18. FDA Approved Drug Products: VFEND (voriconazole) multiple forms/routes [Link]
  19. FDA Label VORICONAZOLE- voriconazole injection [File]
Human Metabolome Database
HMDB0014720
KEGG Drug
D00578
KEGG Compound
C07622
PubChem Compound
71616
PubChem Substance
46506421
ChemSpider
64684
BindingDB
50333117
RxNav
121243
ChEBI
10023
ChEMBL
CHEMBL638
ZINC
ZINC000000014864
Therapeutic Targets Database
DAP001271
PharmGKB
PA10233
PDBe Ligand
VOR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Voriconazole
PDB Entries
3mdt/4uym/4ze0/5hs1/6ay6/6h1o/7ry8/7ry9/7ryb
FDA label
Download (321 KB)
MSDS
Download (57.2 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Completed Not Available Aspergillosis/Candidemia 1
4 Completed Not Available Healthy Subjects (HS) 1
4 Completed Basic Science Fungal Infections 1
4 Completed Diagnostic Drug Drug Interaction (DDI)/Kidney Transplantation 1
4 Completed Health Services Research Healthy Subjects (HS) 2
4 Completed Prevention Prophylaxis Of Invasive Fungal Infections 1
4 Completed Treatment Antimycotic for Systematic Use 1
4 Completed Treatment Aspergillosis/Candidiasis/Cryptococcosis 1
4 Completed Treatment Candidemia/Candidiasis, Invasive 1
4 Completed Treatment Candidiasis 1

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Matrix laboratories ltd
Packagers
  • Cardinal Health
  • DSM Corp.
  • Pfizer Inc.
Dosage Forms
Form Route Strength
Injection, solution Intravenous 200 mg
Tablet, film coated Oral 50 mg
Tablet Oral 200 mg
Powder, for solution Intravenous 200毫克/瓶
Powder, for solution Intravenous 200 MG
Powder, for suspension Oral 200 mg / 5 mL
Tablet Oral 50 mg
Powder Intravenous 200 mg/1vial
Injection, powder, for solution Intravenous 10 mg/ml
Injection, powder, for solution Intravenous
Solution Parenteral 200 mg
Powder, for suspension Oral 40 mg/ml
Tablet, film coated Oral 200 mg
Injection Intravenous
Injection, solution Intravenous
Injection, powder, lyophilized, for solution Intravenous 200 mg
Tablet, film coated Oral
Injection, powder, for solution Parenteral
Tablet, film coated Oral 100 MG
Injection, powder, for solution Intravenous 200 mg
Powder Intravenous 200 mg
Injection, powder, for solution Intravenous 10 mg/1mL
Injection, powder, lyophilized, for solution Intravenous 10 mg/1
Injection, powder, lyophilized, for solution Intravenous 10 mg/1mL
Injection, powder, lyophilized, for solution Intravenous 200 mg/1
Powder, for suspension Oral 40 mg/1mL
Suspension Oral 40 mg/1mL
Tablet Oral 200 mg/1
Tablet Oral 50 mg/1
Tablet, coated Oral 200 mg/1
Tablet, coated Oral 50 mg/1
Tablet, film coated Oral 200 mg/1
Tablet, film coated Oral 50 mg/1
Powder Intravenous 200毫克/瓶
Powder, for solution 200 MG
Powder, for solution
Powder, for suspension Oral
Powder, for solution Parenteral 200 MG
Injection Intravenous 200 mg
Injection Parenteral 200 mg
Injection, solution, concentrate Intravenous 200 mg
Tablet, coated Oral 50 mg
Tablet, coated Oral 200 mg
Powder Intravenous 40 mg/1ml
Injection, powder, for solution Intravenous 200 mg/1vial
Prices
Unit description Cost Unit
Vfend 40 mg/ml Suspension 75ml Bottle 870.72USD bottle
Vfend iv 200 mg vial 143.5USD vial
Vfend 200 mg tablet 49.74USD tablet
Vfend 50 mg tablet 12.43USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region
US5116844 No 1992-05-26 2009-08-11 US flag
CA2295035 No 2005-04-19 2018-06-02 Canada flag
CA2035314 No 2000-01-18 2011-01-30 Canada flag
US5567817 No 1996-10-22 2016-05-24 US flag
US6632803 No 2003-10-14 2018-06-02 US flag

Properties

State
Solid
Experimental Properties
Property Value Source
melting point (°C) 134 °C Pfizer Canada Product Monograph
water solubility Low Patent WO 98/58677
Predicted Properties
Property Value Source
Water Solubility 0.0978 mg/mL ALOGPS
logP 1.65 ALOGPS
logP 1.82 Chemaxon
logS -3.6 ALOGPS
pKa (Strongest Acidic) 12.7 Chemaxon
pKa (Strongest Basic) 2.01 Chemaxon
Physiological Charge 0 Chemaxon
Hydrogen Acceptor Count 5 Chemaxon
Hydrogen Donor Count 1 Chemaxon
Polar Surface Area 76.72 Å2 Chemaxon
Rotatable Bond Count 5 Chemaxon
Refractivity 95.28 m3·mol-1 Chemaxon
Polarizability 30.54 Å3 Chemaxon
Number of Rings 3 Chemaxon
Bioavailability 1 Chemaxon
Rule of Five Yes Chemaxon
Ghose Filter Yes Chemaxon
Veber's Rule No Chemaxon
MDDR-like规则 No Chemaxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.9958
Blood Brain Barrier + 0.9047
Caco-2 permeable + 0.7219
P-glycoprotein substrate Substrate 0.591
P-glycoprotein inhibitor I Non-inhibitor 0.6113
P-glycoprotein inhibitor II Non-inhibitor 0.8195
Renal organic cation transporter Non-inhibitor 0.5354
CYP450 2C9 substrate Non-substrate 0.727
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.5792
CYP450 1A2 substrate Non-inhibitor 0.7491
CYP450 2C9 inhibitor Inhibitor 0.5203
CYP450 2D6 inhibitor Non-inhibitor 0.8315
CYP450 2C19 inhibitor Inhibitor 0.5784
CYP450 3A4 inhibitor Non-inhibitor 0.7011
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6649
Ames test Non AMES toxic 0.7019
Carcinogenicity Non-carcinogens 0.776
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3469 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8791
hERG inhibition (predictor II) Non-inhibitor 0.6282
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
MS/MS Spectrum - , positive LC-MS/MS splash10-0fh9-2593000000-630f0453fb0da8e2745d

Targets

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Details 1.Cytochrome P450 51
Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
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.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
分子量
60674.965 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  2. 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. [Article]
  3. Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G: Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob Agents Chemother. 2005 Feb;49(2):668-79. [Article]
  4. Li X, Brown N, Chau AS, Lopez-Ribot JL, Ruesga MT, Quindos G, Mendrick CA, Hare RS, Loebenberg D, DiDomenico B, McNicholas PM: Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. J Antimicrob Chemother. 2004 Jan;53(1):74-80. Epub 2003 Dec 4. [Article]
  5. Thompson GR 3rd, Lewis JS 2nd: Pharmacology and clinical use of voriconazole. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):83-94. doi: 10.1517/17425250903463878. [Article]
  6. Xu Y, Sheng C, Wang W, Che X, Cao Y, Dong G, Wang S, Ji H, Miao Z, Yao J, Zhang W: Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives. Bioorg Med Chem Lett. 2010 May 1;20(9):2942-5. doi: 10.1016/j.bmcl.2010.03.014. Epub 2010 Mar 7. [Article]
  7. Xu J, Cao Y, Zhang J, Yu S, Zou Y, Chai X, Wu Q, Zhang D, Jiang Y, Sun Q: Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives. Eur J Med Chem. 2011 Jul;46(7):3142-8. doi: 10.1016/j.ejmech.2011.02.042. Epub 2011 Feb 24. [Article]
  8. Sanati H, Belanger P, Fratti R, Ghannoum M: A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. Antimicrob Agents Chemother. 1997 Nov;41(11):2492-6. doi: 10.1128/AAC.41.11.2492. [Article]
  9. VFENDⓇ FDA Label [Link]

Enzymes

Details 1.Dimethylaniline monooxygenase [N-oxide-forming] 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
分子量
60310.285 Da
References
  1. Yanni SB, Annaert PP, Augustijns P, Bridges A, Gao Y, Benjamin DK Jr, Thakker DR: Role of flavin-containing monooxygenase in oxidative metabolism of voriconazole by human liver microsomes. Drug Metab Dispos. 2008 Jun;36(6):1119-25. doi: 10.1124/dmd.107.019646. Epub 2008 Mar 24. [Article]
Details 2.Dimethylaniline monooxygenase [N-oxide-forming] 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
分子量
60032.975 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. 山田T,米诺Y, Naito T,川上J: f的影响lavin-containing monooxygenase 3 and CYP2C19 genotypes on plasma disposition and adverse effects of voriconazole administered orally in immunocompromised patients. J Infect Chemother. 2019 Dec;25(12):1019-1025. doi: 10.1016/j.jiac.2019.05.032. Epub 2019 Jun 22. [Article]
  3. Yanni SB, Annaert PP, Augustijns P, Ibrahim JG, Benjamin DK Jr, Thakker DR: In vitro hepatic metabolism explains higher clearance of voriconazole in children versus adults: role of CYP2C19 and flavin-containing monooxygenase 3. Drug Metab Dispos. 2010 Jan;38(1):25-31. doi: 10.1124/dmd.109.029769. [Article]
  4. Yanni SB, Annaert PP, Augustijns P, Bridges A, Gao Y, Benjamin DK Jr, Thakker DR: Role of flavin-containing monooxygenase in oxidative metabolism of voriconazole by human liver microsomes. Drug Metab Dispos. 2008 Jun;36(6):1119-25. doi: 10.1124/dmd.107.019646. Epub 2008 Mar 24. [Article]
Details 3.Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
分子量
57108.065 Da
References
  1. Jeong S, Nguyen PD, Desta Z: Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother. 2009 Feb;53(2):541-51. doi: 10.1128/AAC.01123-08. Epub 2008 Nov 24. [Article]
  2. Yamazaki H, Nakamoto M, Shimizu M, Murayama N, Niwa T: Potential impact of cytochrome P450 3A5 in human liver on drug interactions with triazoles. Br J Clin Pharmacol. 2010 Jun;69(6):593-7. doi: 10.1111/j.1365-2125.2010.03656.x. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Details 4.Cytochrome P450 3A7
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
分子量
57525.03 Da
References
  1. Jeong S, Nguyen PD, Desta Z: Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother. 2009 Feb;53(2):541-51. doi: 10.1128/AAC.01123-08. Epub 2008 Nov 24. [Article]
  2. Flockhart Table of Drug Interactions [Link]
Details 5.Cytochrome P450 2C19
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
分子量
55930.545 Da
References
  1. Hyland R, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos. 2003 May;31(5):540-7. [Article]
  2. Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H: Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6. doi: 10.1016/j.bcp.2007.03.012. Epub 2007 Mar 19. [Article]
  3. Jeong S, Nguyen PD, Desta Z: Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother. 2009 Feb;53(2):541-51. doi: 10.1128/AAC.01123-08. Epub 2008 Nov 24. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  6. VFENDⓇ FDA Label [Link]
Details 6.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
分子量
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Jeong S, Nguyen PD, Desta Z: Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother. 2009 Feb;53(2):541-51. doi: 10.1128/AAC.01123-08. Epub 2008 Nov 24. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. VFENDⓇ FDA Label [Link]
Details 7.Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
分子量
55627.365 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. Flockhart Table of Drug Interactions [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. VFENDⓇ FDA Label [Link]
Details 8.Cytochrome P450 2B6
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
分子量
56277.81 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Details 9.Prostaglandin G/H synthase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
分子量
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 19, 2023 09:30