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Showing drug card for Voriconazole (DB00582)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:14
Primary Accession Number DB00582
Secondary Accession Number
  • APRD00543
Name Voriconazole
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Voriconazole (Vfend®, Pfizer) is a triazole antifungal medication used to treat serious fungal infections. 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.
Synonyms
  1. VCZ
  2. voriconazole
Brand Names
  1. Vfend
Brand Mixtures Not Available
Chemical IUPAC Name (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
Chemical Formula C16H14F3N5O
Chemical Structure Structure
CAS Registry Number 137234-62-9
InChI Identifier InChI=1/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
InChI Key BCEHBSKCWLPMDN-MGPLVRAMBL
KEGG Drug D00578 Link Image
KEGG Compound C07622 Link Image
PubChem Compound 71616 Link Image
PubChem Substance 213886 Link Image
ChEBI ID Not Available
PharmGKB ID PA10233 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02256460 Link Image
RxList Link http://www.rxlist.com/cgi/generic/vfend.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Voriconazole Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 349.3105
Monoisotopic Molecular Weight 349.1150
State Solid
Melting Point 127 - 130 oC
Experimental Water Solubility Low Source: PhysProp
Predicted Water Solubility 9.78e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1 Source: PhysProp
Predicted LogP 1.65 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.55 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@@H](C1=NC=NC=C1F)[C@](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1
Canonical SMILES CC(C1=NC=NC=C1F)C(O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1
Drug Category
  • Antifungal Agents
  • Antifungals
ATC Codes
AHFS Codes
  • 08:14.08
Indication For the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.
Pharmacology Voriconazole is a triazole antifungal agent indicated for use in the treatment of fungal infections including invasive aspergillosis, esophageal candidiasis, and serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani. Fungal plasma membranes are similar to mammalian plasma membranes, differing in having the nonpolar sterol ergosterol, rather than cholesterol, as the principal sterol. Membrane sterols such as ergosterol provide structure, modulation of membrane fluidity, and possibly control of some physiologic events. Voriconazole effects the formation of the fungal plasma membrane by indirectly inhibiting the biosynthesis of ergosterol. This results in plasma membrane permeability changes and inhibition of growth.
Mechanism of Action Voriconazole binds and inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-alpha sterol demethylase. The inhibition of 14-alpha sterol demethylase results in a depletion of ergosterol in fungal cell membrane.
Absorption The oral bioavailability is estimated to be 96% (CV 13%).
Toxicity The minimum lethal oral dose in mice and rats was 300 mg/kg (equivalent to 4 and 7 times the recommended maintenance dose (RMD), based on body surface area). At this dose, clinical signs observed in both mice and rats included salivation, mydriasis, titubation (loss of balance while moving), depressed behavior, prostration, partially closed eyes, and dyspnea. Other signs in mice were convulsions, corneal opacification and swollen abdomen.
Protein Binding 58%
Biotransformation Hepatic. The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma. Since this metabolite has minimal antifungal activity, it does not contribute to the overall efficacy of voriconazole.
Half Life Not Available
Dosage Forms
Form Route
Solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. 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. [PubMed Link Image]
  2. 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. [PubMed Link Image]
  3. 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. [PubMed Link Image]
  4. 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. [PubMed Link Image]
  5. 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. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Yeast and other fungi
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C19 (CYP2C19)
  2. Cytochrome P450 3A4 (CYP3A4)
  3. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. Cytochrome P450 51
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C19 (CYP2C19)
Enzyme 1 Gene Name CYP2C19
Enzyme 1 SwissProt ID P33261 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80) 
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 2 Gene Name CYP3A4
Enzyme 2 SwissProt ID P08684 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 3 Gene Name CYP2C9
Enzyme 3 SwissProt ID P11712 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 249
Target 1 Name Cytochrome P450 51
Target 1 Synonyms
  1. CYPLI
  2. EC 1.14.13.70
  3. Lanosterol 14-alpha demethylase
  4. P450-14DM
  5. P450-LIA1
  6. Sterol 14- alpha demethylase
Target 1 Gene Name ERG11
Target 1 Protein Sequence >Cytochrome P450 51 
MSATKSIVGEALEYVNIGLSHFLALPLAQRISLIIIIPFIYNIVWQLLYSLRKDRPPLVF
YWIPWVGSAVVYGMKPYEFFEECQKKYGDIFSFVLLGRVMTVYLGPKGHEFVFNAKLADV
SAEAAYAHLTTPVFGKGVIYDCPNSRLMEQKKFVKGALTKEAFKSYVPLIAEEVYKYFRD
SKNFRLNERTTGTIDVMVTQPEMTIFTASRSLLGKEMRAKLDTDFAYLYSDLDKGFTPIN
FVFPNLPLEHYRKRDHAQKAISGTYMSLIKERRKNNDIQDRDLIDSLMKNSTYKDGVKMT
DQEIANLLIGVLMGGQHTSAATSAWILLHLAERPDVQQELYEEQMRVLDGGKKELTYDLL
QEMPLLNQTIKETLRMHHPLHSLFRKVMKDMHVPNTSYVIPAGYHVLVSPGYTHLRDEYF
PNAHQFNIHRWNKDSASSYSVGEEVDYGFGAISKGVSSPYLPFGGGRHRCIGEHFAYCQL
GVLMSIFIRTLKWHYPEGKTVPPPDFTSMVTLPTGPAKIIWEKRNPEQKI
Target 1 Number of Residues 538
Target 1 Molecular Weight 60721
Target 1 Theoretical pI 8.95
Target 1 GO Classification
Function
tetrapyrrole binding
heme binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 1 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 1 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
Target 1 Pathways Not Available
Target 1 Reactions
  • obtusifoliol + 3 O2 + 3 NADPH + 3 H+ = 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + 3 NADP+ + 4 H2O
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 21-41
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 170946 Link Image
Target 1 UniProtKB/Swiss-Prot ID P10614 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CP51_YEAST Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1593 bp 
ATGTCTGCTACCAAGTCAATCGTTGGAGAGGCATTGGAATACGTAAACATTGGTTTAAGT
CATTTCTTGGCTTTACCATTGGCCCAAAGAATCTCTTTGATCATAATAATTCCTTTCATT
TACAATATTGTATGGCAATTACTATATTCTTTGAGAAAGGACCGTCCACCTCTAGTGTTT
TACTGGATTCCATGGGTCGGTAGTGCTGTTGTGTACGGTATGAAGCCATACGAGTTTTTC
GAAGAATGTCAAAAGAAATACGGTGATATTTTTTCATTCGTTTTGTTAGGAAGAGTCATG
ACTGTGTATTTAGGACCAAAGGGTCACGAATTTGTCTTCAACGCTAAGTTGGCAGATGTT
TCAGCAGAAGCTGCTTACGCTCATTTGACTACTCCAGTTTTCGGTAAAGGTGTTATTTAC
GATTGTCCAAATTCTAGATTGATGGAGCAAAAGAAGTTTGTTAAGGGTGCTCTAACCAAA
GAAGCCTTCAAGAGCTACGTTCCATTGATTGCTGAAGAAGTGTACAAGTACTTCAGAGAC
TCCAAAAACTTCCGTTTGAATGAAAGAACTACTGGTACTATTGACGTGATGGTTACTCAA
CCTGAAATGACTATTTTCACCGCTTCAAGATCATTATTGGGTAAGGAAATGAGAGCAAAA
TTGGATACCGATTTTGCTTACTTGTACAGTGATTTGGATAAGGGTTTCACTCCAATCAAC
TTCGTCTTCCCTAACTTACCATTGGAACACTATAGAAAGAGAGATCACGCTCAAAAGGCT
ATCTCCGGTACTTACATGTCTTTGATTAAGGAAAGAAGAAAGAACAACGACATTCAAGAC
AGAGATTTGATCGATTCCTTGATGAAGAACTCTACCTACAAGGATGGTGTGAAGATGACT
GATCAAGAAATCGCTAACTTGTTAATTGGTGTCTTAATGGGTGGTCAACATACTTCTGCT
GCCACTTCTGCTTGGATTTTGTTGCACTTGGCTGAAAGACCAGATGTCCAACAAGAATTG
TACGAAGAACAAATGCGTGTTTTGGATGGTGGTAAGAAGGAATTGACCTACGATTTATTA
CAAGAAATGCCATTGTTGAACCAAACTATTAAGGAAACTCTAAGAATGCACCATCCATTG
CACTCTTTGTTCCGTAAGGTTATGAAAGATATGCACGTTCCAAACACTTCTTATGTCATC
CCAGCAGGTTATCACGTTTTGGTTTCTCCAGGTTACACTCATTTAAGAGACGAATACTTC
CCTAATGCTCACCAATTCAACATTCACCGTTGGAACAAAGATTCTGCCTCCTCTTATTCC
GTCGGTGAAGAAGTCGATTACGGTTTCGGTGCCATTTCTAAGGGTGTCAGCTCTCCATAC
TTACCTTTCGGTGGTGGTAGACACAGATGTATCGGTGAACACTTTGCTTACTGTCAGCTA
GGTGTTCTAATGTCCATTTTTATCAGAACATTAAAATGGCATTACCCAGAGGGTAAGACC
GTTCCACCTCCTGACTTTACATCTATGGTTACTCTTCCAACCGGTCCAGCCAAGATCATC
TGGGAAAAGAGAAATCCAGAACAAAAGATCTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature. 2003 Oct 16;425(6959):737-41. [PubMed Link Image]
  2. Ishida N, Aoyama Y, Hatanaka R, Oyama Y, Imajo S, Ishiguro M, Oshima T, Nakazato H, Noguchi T, Maitra US, et al.: A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS. Biochem Biophys Res Commun. 1988 Aug 30;155(1):317-23. [PubMed Link Image]
  3. Kalb VF, Woods CW, Turi TG, Dey CR, Sutter TR, Loper JC: Primary structure of the P450 lanosterol demethylase gene from Saccharomyces cerevisiae. DNA. 1987 Dec;6(6):529-37. [PubMed Link Image]
  4. Kalb VF, Loper JC, Dey CR, Woods CW, Sutter TR: Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae. Gene. 1986;45(3):237-45. [PubMed Link Image]
  5. Johnston M, Andrews S, Brinkman R, Cooper J, Ding H, Dover J, Du Z, Favello A, Fulton L, Gattung S, et al.: Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science. 1994 Sep 30;265(5181):2077-82. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. 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. [PubMed Link Image]
  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. [PubMed Link Image]
  4. 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 Link Image]
  5. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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.