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Showing drug card for Fosamprenavir (DB01319)

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Version 2.5
Creation Date 2007-06-30 17:17:40
Update Date 2009-06-23 18:08:09
Primary Accession Number DB01319
Secondary Accession Number Not Available
Name Fosamprenavir
Drug Type
  • Approved
  • Small Molecule
Description Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease.
Synonyms Not Available
Brand Names
  1. Lexiva
  2. Telzir
Brand Mixtures Not Available
Chemical IUPAC Name [(3S)-oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-1-phenyl-3-phosphonooxybutan-2-yl]carbamate
Chemical Formula C25H36N3O9PS
Chemical Structure Structure
CAS Registry Number 226700-79-4
InChI Identifier InChI=1/C25H36N3O9PS/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32)/t21-,23-,24+/m0/s1/f/h27,30-31H
InChI Key MLBVMOWEQCZNCC-ARLDYLSADF
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound 131536 Link Image
PubChem Substance 10242897 Link Image
ChEBI ID Not Available
PharmGKB ID PA10084 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02261545 Link Image
RxList Link http://www.rxlist.com/cgi/generic/lexiva.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Fosamprenavir Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 585.6070
Monoisotopic Molecular Weight 585.1910
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 6.85e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP 0.84 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.93 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 CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1
Canonical SMILES CC(C)CN(CC(OP(O)(O)=O)C(CC1=CC=CC=C1)NC(=O)OC1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1
Drug Category
  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Prodrugs
ATC Codes
AHFS Codes
  • 08:18.08.08
Indication Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection.
Pharmacology Fosamprenavir is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reducing the number of pills required versus standard amprenavir.
Mechanism of Action Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.
Absorption The absolute oral bioavailability of amprenavir after administration of fosamprenavir in humans has not been established. After administration of a single 1,400 mg dose in the fasted state, fosamprenavir oral suspension (50 mg/mL) and fosamprenavir tablets (700 mg) provided similar amprenavir exposures (AUC), however, the Cmax of amprenavir after administration of the suspension formulation was 14.5 % higher compared with the tablet.
Toxicity Not Available
Protein Binding Very high (approximately 90%); primarily bound to alpha 1 -acid glycoprotein. Higher amounts of unbound amprenavir present as amprenavir serum concentrations increase.
Biotransformation In the gut epithelium during absorption, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system.
Half Life The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours.
Dosage Forms
Form Route
Suspension Oral
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Not Available
Drug Interactions
Drug Interaction
Acenocoumarol The protease inhibitor increases the anticoagulant effect
Alprazolam Amprenavir increases the effect and toxicity of benzodiazepine
Aluminium The antiacid decreases the absorption of amprenavir
Amiodarone The protease inhibitor increases the effect and toxicity of amiodarone
Anisindione The protease inhibitor increases the anticoagulant effect
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Amprenavir can possibly increase the statin toxicity
Bepridil Amprenavir increases the effect and toxicity of bepridil
Bismuth The antiacid decreases the absorption of amprenavir
Calcium The antiacid decreases the absorption of amprenavir
Cisapride Amprenavir increases the effect and toxicity of cisapride
Clorazepate Amprenavir increases the effect and toxicity of benzodiazepine
Cyclosporine The protease inhibitor increases the effect of cyclosporine
Delavirdine Decreased levels of delavirdine with increased levels of amprenavir
Diazepam Amprenavir increases the effect and toxicity of benzodiazepine
Dicumarol The protease inhibitor increases the anticoagulant effect
Dihydroergotamine Amprenavir increases the effect and toxicity of ergot derivative
Ergotamine Amprenavir increases the effect and toxicity of ergot derivative
Fentanyl The protease inhibitor increases the effect and toxicity of fentanyl
Flurazepam Amprenavir increases the effect and toxicity of benzodiazepine
Fusidic Acid The protease inhibitor increases the effect and toxicity of fusidic acid
Lovastatin Amprenavir can possibly increase the statin toxicity
Magnesium The antiacid decreases the absorption of amprenavir
Magnesium oxide The antiacid decreases the absorption of amprenavir
Methadone The protease inhibitor decreases the effect of methadone
Midazolam Amprenavir increases the effect and toxicity of benzodiazepine
Pimozide Amprenavir increases the effect and toxicity of pimozide
Ranolazine Increased levels of ranolazine - risk of toxicity
Rifabutin Amprenavir increases the effect and toxicity of rifabutin
Rifampin In presence of rifampin anticipate decrease of amprenavir efficiency
Sildenafil The protease inhibitor increases the effect and toxicity of sildenafil
Simvastatin Amprenavir can possibly increase the statin toxicity
St. John's Wort St. John's Wort decreases the effect of indinavir
Tacrolimus The protease inhibitor increases the effect and toxicity of tacrolimus
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Triazolam Amprenavir increases the effect and toxicity of benzodiazepine
Vardenafil The protease inhibitor increases the effect and toxicity of
Warfarin The protease inhibitor increases the anticoagulant effect
Food Interactions
  • Avoid alcohol, especially with the oral solution since it contains propylene glycol which competes with alcohol for alcohol dehydrogenase metabolism.
  • Take with or without food, however avoid lipid-rich meals.
  • Vitamin E increases fosamprenavir bioavailability.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Human Immunodeficiency Virus
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. HIV-1 protease
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 731
Target 1 Name HIV-1 protease
Target 1 Synonyms
  1. Fragment
Target 1 Gene Name HIV-1 protease
Target 1 Protein Sequence >HIV-1 protease 
PQVTLWQRPIVTIKIGGQLKEALLDTGADDTVLEEMSLPGKWKPKMIGGIGGFIKVRQYD
QVSIEICGHKAIGTVLIGPTPVNIIGRNLLTQLGCTLNF
Target 1 Number of Residues 100
Target 1 Molecular Weight 10725
Target 1 Theoretical pI 8.77
Target 1 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
aspartic-type endopeptidase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 1 General Function Involved in aspartic-type endopeptidase activity
Target 1 Specific Function Not Available
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 4377614 Link Image
Target 1 UniProtKB/Swiss-Prot ID O90777 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name O90777_9PLVG Link Image
Target 1 PDB ID 1ODW Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >297 bp 
CCTCAGGTCACTCTTTGGCAACGACCCATAGTCACAATAAAGATAGGGGGGCAACTAAAG
GAAGCTCTATTAGATACAGGAGCAGATGATACAGTATTAGAAGAAATGAGTTTGCCAGGA
AAATGGAAACCAAAAATGATAGGGGGAATTGGAGGTTTTATCAAAGTAAGACAGTATGAT
CAGGTATCCATAGAAATCTGCGGACATAAAGCTATAGGTACAGTATTAATAGGACCTACA
CCTGTCAACATAATTGGAAGGAATCTGTTGACTCAGCTTGGCTGCACTTTAAATTTT
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. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. J Clin Microbiol. 2001 Feb;39(2):454-9. [PubMed Link Image]
  2. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. Antimicrob Agents Chemother. 2001 Mar;45(3):893-900. [PubMed Link Image]
Target 1 Drug 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. [PubMed Link Image]
  2. 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.