Voriconazole

Identification

Summary

Voriconazole is 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.14 It 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 some fluconazole-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
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

For the treatment of esophageal candidiasis, cadidemia, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.13,14

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAspergillosis of the central nervous system••• •••••
Treatment ofAspergillosis of the liver••• •••••
Treatment ofCandidemia•••••••••••••••••• ••••••••••••••••••
Treatment ofCandidemia•••••••••••••••••• •••••••••••••••••••• ••••••
Treatment ofCandidiasis••• •••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth.13 It 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 including Aspergillus spp. and Candida spp. Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens.11,10,13 Like 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.

TargetActionsOrganism
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 diet 6. 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/kg 13. Population pharmacokinetic studies estimate the median volume of distribution to be 77.6 L with the central compartment estimated at 1.07 L/kg 6 Voriconazole 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 proteins 13.

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 CYP2C19.8 Voriconazole N-oxide is the major circulating metabolite, accounting for 72% of radiolabeled metabolites found.13 CYP3A4 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 CYP3A4.8 CYP3A5 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

Voriconazole is eliminated via 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.13,14 In 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/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYPC19*17(T;T) / (C;T)C > TEffect Directly StudiedPatients with this genotype in CYP2C19 are ultra fast metabolizers and require higer doses of voriconazole to attain the therapeutic effect.Details
Cytochrome P450 2C19CYP2C19*2Not Available681G>ADirectly Studied EffectThe presence of this polymorphism in CYP2C19 is associated with poor metabolism of voriconazole.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>ADirectly Studied EffectThe presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of voriconazole.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be increased when it is combined with Voriconazole.
AbametapirThe serum concentration of Voriconazole can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Voriconazole can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Voriconazole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Voriconazole.
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
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VfendTablet, film coated200 mgOralPfizer Europe Ma Eeig2021-02-11Not applicableEU flag
VfendTablet, film coated200 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
VfendInjection, powder, for solution200 mgIntravenousPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
VfendTablet, film coated200 mgOralPfizer Europe Ma Eeig2021-02-11Not applicableEU flag
VfendTablet, film coated50 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-voriconazoleTablet200 mgOralAccord Healthcare IncNot applicableNot applicableCanada flag
Ach-voriconazoleTablet50 mgOralAccord Healthcare IncNot applicableNot applicableCanada flag
Apo-voriconazoleTablet50 mgOralApotex Corporation2014-04-14Not applicableCanada flag
Apo-voriconazoleTablet200 mgOralApotex Corporation2014-04-14Not applicableCanada flag
Auro-voriconazoleTablet200 mgOralAuro Pharma IncNot applicableNot applicableCanada flag

Categories

ATC Codes
J02AC03 — Voriconazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
General References
  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 JA, Abdel-Rahman SM: Voriconazole: a new triazole 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 Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableAspergillosis / Candidemia1
4CompletedNot AvailableHealthy Volunteers (HV)1
4CompletedBasic ScienceFungal Infections1
4CompletedDiagnosticDrug Drug Interaction (DDI) / Kidney Transplantation1
4CompletedHealth Services ResearchHealthy Volunteers (HV)2

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Matrix laboratories ltd
Packagers
  • Cardinal Health
  • DSM Corp.
  • Pfizer Inc.
Dosage Forms
FormRouteStrength
SolutionIntravenous200.00 mg
Injection, powder, lyophilized, for solutionIntravenous20000000 mg
Tablet, coatedOral5000000 mg
SolutionIntravenous220.000 mg
Powder, for solutionIntravenous200 mg / vial
Powder, for solutionIntravenous200 MG
Powder, for suspensionOral200 mg / 5 mL
SolutionIntravenous200.000 mg
TabletOral200 mg
TabletOral200.000 mg
TabletOral50 mg
PowderIntravenous200 mg/1vial
Tablet, film coatedOral200 MG
Tablet, film coatedOral50 MG
Injection, powder, for solutionIntravenous10 mg/ml
Injection, powder, for solutionIntravenous
SolutionParenteral200 mg
Powder, for suspensionOral40 mg/ml
InjectionIntravenous
Injection, solutionIntravenous200 mg
Injection, powder, lyophilized, for solutionIntravenous200 mg
Tablet, film coatedOral
Injection, powder, for solutionParenteral
Tablet, film coatedOral100 MG
Injection, powder, for solutionIntravenous200 mg
PowderIntravenous200 mg
Injection, powder, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous200 mg/1
Powder, for suspensionOral40 mg/1mL
SuspensionOral40 mg/1mL
TabletOral200 mg/1
TabletOral50 mg/1
Tablet, coatedOral200 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral50 mg/1
Powder, for solution200 MG
Powder, for solution
Powder, for suspensionOral
Powder, for solutionParenteral200 MG
InjectionIntravenous200 mg
Injection, solutionIntravenous
InjectionParenteral200 mg
Injection, solution, concentrateIntravenous200 mg
Tablet, coatedOral50 mg
Tablet, coatedOral200 mg
PowderIntravenous40 mg/1ml
Injection, powder, for solutionIntravenous200 mg/1vial
Prices
Unit descriptionCostUnit
Vfend 40 mg/ml Suspension 75ml Bottle870.72USD bottle
Vfend iv 200 mg vial143.5USD vial
Vfend 200 mg tablet49.74USD tablet
Vfend 50 mg tablet12.43USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5116844No1992-05-262009-08-11US flag
CA2295035No2005-04-192018-06-02Canada flag
CA2035314No2000-01-182011-01-30Canada flag
US5567817No1996-10-222016-05-24US flag
US6632803No2003-10-142018-06-02US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)134 °CPfizer Canada Product Monograph
water solubilityLowPatent WO 98/58677
Predicted Properties
PropertyValueSource
Water Solubility0.0978 mg/mLALOGPS
logP1.65ALOGPS
logP1.82Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.7Chemaxon
pKa (Strongest Basic)2.01Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area76.72 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity95.28 m3·mol-1Chemaxon
Polarizability30.54 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.9047
Caco-2 permeable+0.7219
P-glycoprotein substrateSubstrate0.591
P-glycoprotein inhibitor INon-inhibitor0.6113
P-glycoprotein inhibitor IINon-inhibitor0.8195
Renal organic cation transporterNon-inhibitor0.5354
CYP450 2C9 substrateNon-substrate0.727
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5792
CYP450 1A2 substrateNon-inhibitor0.7491
CYP450 2C9 inhibitorInhibitor0.5203
CYP450 2D6 inhibitorNon-inhibitor0.8315
CYP450 2C19 inhibitorInhibitor0.5784
CYP450 3A4 inhibitorNon-inhibitor0.7011
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6649
Ames testNon AMES toxic0.7019
CarcinogenicityNon-carcinogens0.776
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3469 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8791
hERG inhibition (predictor II)Non-inhibitor0.6282
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-007o-9870000000-37f0e72d184d58adf95f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fh9-2593000000-630f0453fb0da8e2745d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0009000000-5e1fd7a492eb9140a04c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ufr-0295000000-82f1472058b32dfa796e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9023000000-3b8844533ee93a082994
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-6294000000-e7b8ea60d52357ffb05f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9032000000-a4c30afef56f1d8e1c85
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pb9-5972000000-2b77ac407b4417dbfcb0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-180.1663041
predicted
DarkChem Lite v0.1.0
[M-H]-174.20804
predicted
DeepCCS 1.0 (2019)
[M+H]+179.6872041
predicted
DarkChem Lite v0.1.0
[M+H]+176.56604
predicted
DeepCCS 1.0 (2019)
[M+Na]+179.9632041
predicted
DarkChem Lite v0.1.0
[M+Na]+183.12534
predicted
DeepCCS 1.0 (2019)

Targets

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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
Molecular Weight
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

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
Molecular Weight
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]
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
Molecular Weight
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. Yamada T, Mino Y, Naito T, Kawakami J: Impact of flavin-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]
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
Molecular Weight
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]
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
Molecular Weight
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
Molecular Weight
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]
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. 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
Molecular Weight
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]
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. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
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
Molecular Weight
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 March 18, 2024 16:48