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Showing drug card for Amprenavir (DB00701)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:24
Primary Accession Number DB00701
Secondary Accession Number
  • APRD00605
Name Amprenavir
Drug Type
  • Approved
  • Small Molecule
Description Amprenavir is a protease inhibitor used to treat HIV infection.
Synonyms
  1. AMP
  2. AMV
  3. APV
  4. VX-478
Brand Names
  1. Agenerase
  2. Prozei
  3. Vertex
Brand Mixtures Not Available
Chemical IUPAC Name [(3S)-oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
Chemical Formula C25H35N3O6S
Chemical Structure Structure
CAS Registry Number 161814-49-9
InChI Identifier InChI=1/C25H35N3O6S/c1-18(2)15-28(35(31,32)22-10-8-20(26)9-11-22)16-24(29)23(14-19-6-4-3-5-7-19)27-25(30)34-21-12-13-33-17-21/h3-11,18,21,23-24,29H,12-17,26H2,1-2H3,(H,27,30)/t21-,23-,24+/m0/s1/f/h27H
InChI Key YMARZQAQMVYCKC-RGRKSSPIDA
KEGG Drug D00894 Link Image
KEGG Compound C08086 Link Image
PubChem Compound 65016 Link Image
PubChem Substance 7847958 Link Image
ChEBI ID 2684 Link Image
PharmGKB ID PA448422 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02243542 Link Image
RxList Link http://www.rxlist.com/cgi/generic/ampren.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/age1526.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Amprenavir Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 505.6270
Monoisotopic Molecular Weight 505.2247
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 4.91e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP 1.85 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.01 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 1ODW Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(C)CN(C[C@@H](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(O)C(CC1=CC=CC=C1)NC(=O)OC1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1
Drug Category
  • Anti-HIV Agents
  • Antibiotics, Antitubercular
  • HIV Protease Inhibitors
ATC Codes
AHFS Codes
  • 08:18.08.08
Indication For the treatment of HIV-1 infection in combination with other antiretroviral agents.
Pharmacology Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism of Action Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Absorption Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (Tmax) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.
Toxicity Not Available
Protein Binding Very high (90%). Amprenavir has the highest affinity for alpha(1)-acid glycoprotein.
Biotransformation Hepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces.
Half Life 7.1-10.6 hours
Dosage Forms
Form Route
Capsule Oral
Liquid Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Increases the anticoagulant effect
Alprazolam 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 Increases the anticoagulant effect
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Amprenavir can possibly increase the statin toxicity
Bepridil Increases the effect and toxicity of bepridil
Bismuth Subsalicylate The antiacid decreases the absorption of amprenavir
Calcium The antiacid decreases the absorption of amprenavir
Cisapride Increases the effect and toxicity of cisapride
Clorazepate 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 Increases the effect and toxicity of benzodiazepine
Dicumarol Increases the anticoagulant effect
Dihydroergotamine Increases the effect and toxicity of ergot derivative
Dihydroxyaluminium The antiacid decreases the absorption of amprenavir
Disulfiram Increased irsk of side effects (oral solution)
Ergotamine Increases the effect and toxicity of ergot derivative
Ethinyl Estradiol Ritonavir could decrease the contraceptive efficacy
Fentanyl The protease inhibitor increases the effect and toxicity of fentanyl
Flurazepam Increases the effect and toxicity of benzodiazepine
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
Mestranol Ritonavir could decrease the contraceptive efficacy
Methadone The protease inhibitor decreases the effect of methadone
Metronidazole Increased risk of side effects (oral solution)
Midazolam Increases the effect and toxicity of benzodiazepine
Pimozide Increases the effect and toxicity of pimozide
Ranolazine Increased levels of ranolazine- risk of toxicity
Rifabutin 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 increase the effect and toxicity of tacrolimus
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Triazolam Increases the effect and toxicity of benzodiazepine
Vardenafil The protease inhibitor increases the effect adn toxicity of vardenafil
Vitamin E Increased serum levels of vitamin E
Warfarin 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 amprenavir bioavailability.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
  4. PDRhealth 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]
  3. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Next Generation Protease Inhibitor of Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2007 Jul 16;. [PubMed Link Image]
  4. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2007 Sep 11;. [PubMed Link Image]
  5. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to HIV-1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Oct 10;. [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.