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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H36N3O9PS
Molecular Weight 585.607
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSAMPRENAVIR

SMILES

CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)S(=O)(=O)C3=CC=C(N)C=C3

InChI

InChIKey=MLBVMOWEQCZNCC-OEMFJLHTSA-N
InChI=1S/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

HIDE SMILES / InChI

Molecular Formula C25H36N3O9PS
Molecular Weight 585.607
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23519392 | https://www.ncbi.nlm.nih.gov/pubmed/11152018 | https://www.ncbi.nlm.nih.gov/pubmed/15341507

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. Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). Fosamprenavir (GW433908, Lexiva, Telzir) is an oral prodrug of amprenavir, with a reduced daily pill burden. The use of protease inhibitors has also been associated with dyslipidemia and an increased risk of cardiovascular disease. Amprenavir activates Pregnane X receptor to mediate dyslipidemia.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AGENERASE

Approved Use

AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Launch Date

9.2404803E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.36 μg/mL
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6.18 μg/mL
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
9.72 μg/mL
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
6.77 μg/mL
20 mg/kg bw 2 times / day multiple, oral
dose: 20 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
3.99 μg/mL
15 mg/kg bw 3 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
18.5 μg × h/mL
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
22.06 μg × h/mL
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
28.05 μg × h/mL
1200 mg single, oral
dose: 1200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
15.46 μg × h/mL
20 mg/kg bw 2 times / day multiple, oral
dose: 20 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
8.73 μg × h/mL
15 mg/kg bw 3 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.85 h
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMPRENAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea (12%)
Vomiting (6%)
Loose stools (3%)
Abdominal pain (2%)
Abdominal discomfort (2%)
Rash (3%)
Sources: Page: p.1387
1200 mg single, oral
Recommended
Dose: 1200 mg
Route: oral
Route: single
Dose: 1200 mg
Sources: Page: p.1688
unhealthy, 33+/-6.7
n = 12
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 33+/-6.7
Sex: M+F
Population Size: 12
Sources: Page: p.1688
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources: Page: p.11
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.11
Disc. AE: Reaction skin, Stevens-Johnson syndrome...
AEs leading to
discontinuation/dose reduction:
Reaction skin (grade 3-4)
Stevens-Johnson syndrome (grade 3-4)
Sources: Page: p.11
AEs

AEs

AESignificanceDosePopulation
Nausea 12%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Abdominal discomfort 2%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Abdominal pain 2%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Loose stools 3%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Rash 3%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Vomiting 6%
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Co-administed with::
lamivudine, po(150 mg, BID)
zidovudine, po(300 mg, BID)
Sources: Page: p.1387
unhealthy, 21-62
n = 113
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21-62
Sex: M+F
Population Size: 113
Sources: Page: p.1387
Reaction skin grade 3-4
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources: Page: p.11
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.11
Stevens-Johnson syndrome grade 3-4
Disc. AE
1200 mg 2 times / day multiple, oral
Recommended
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources: Page: p.11
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.11
PubMed

PubMed

TitleDatePubMed
Four new antiretroviral medications will soon offer more options to HIV patients.
1998 Jul-Aug
Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir.
2000 Aug
Inhibition of HIV-1 protease by a boron-modified polypeptide.
2000 Oct 1
In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632.
2000 Sep
Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease.
2000 Sep 21
Development of HIV protease inhibitors: a survey.
2001
Metabolic disposition and pharmacokinetics of [14C]-amprenavir, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a single oral dose to healthy male subjects.
2001 Apr
[Determining resistance in HIV therapy. Careful interpretation only].
2001 Apr 2
Liquid chromatographic-tandem mass spectrometric determination of amprenavir (agenerase) in serum/plasma of human immunodeficiency virus type-1 infected patients receiving combination antiretroviral therapy.
2001 Apr 20
Antiretrovirals: simultaneous determination of five protease inhibitors and three nonnucleoside transcriptase inhibitors in human plasma by a rapid high-performance liquid chromatography--mass spectrometry assay.
2001 Aug
Safety profile and tolerability of amprenavir in patients enrolled in an early access program.
2001 Feb
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.
2001 Feb
Possible linkage of amprenavir with intracranial bleeding in an HIV-infected hemophiliac.
2001 Jul
High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction.
2001 Jul 15
Synthesis of a chiral aziridine derivative as a versatile intermediate for HIV protease inhibitors.
2001 Jul 26
Amprenavir: new preparation. Another HIV protease inhibitor: no proven advance.
2001 Jun
A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience.
2001 Jun
Phase III trials for new PI.
2001 Mar
Pharmacokinetics and safety of amprenavir and ritonavir following multiple-dose, co-administration to healthy volunteers.
2001 May 25
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.
2001 May 5
[Drug interactions with antiretroviral agents].
2001 May-Jun
In vitro activity of amprenavir against Pneumocystis carinii.
2001 Sep
Retroviral proteases.
2002
New dosing regimen approved.
2002 Apr
Simultaneous determination of the six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus M8 nelfinavir metabolite and the nonnucleoside reverse transcription inhibitor efavirenz in human plasma by solid-phase extraction and column liquid chromatography.
2002 Apr
HIV-1 genotype and phenotype correlate with virological response to abacavir, amprenavir and efavirenz in treatment-experienced patients.
2002 Feb 15
Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors.
2002 Feb 22
Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.
2002 Jan 25
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002 Jul
The pharmacokinetics of amprenavir, zidovudine, and lamivudine in the genital tracts of men infected with human immunodeficiency virus type 1 (AIDS clinical trials group study 850).
2002 Jul 15
High-performance liquid chromatographic method for the simultaneous determination of the six HIV-protease inhibitors and two non-nucleoside reverse transcriptase inhibitors in human plasma.
2002 Jun
Fosamprenavir. Vertex Pharmaceuticals/GlaxoSmithKline.
2002 Mar
Drug interactions between HIV protease inhibitors based on physiologically-based pharmacokinetic model.
2002 Mar
Efavirenz-induced skin eruption and successful desensitization.
2002 Mar
FDA approves new dosing for amprenavir and ritonavir combination.
2002 Mar 8
Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.
2002 Mar-Apr
Patents

Sample Use Guides

Adults: The recommended oral dose of AGENERASE Capsules for adults is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. Concomitant Therapy: If AGENERASE and ritonavir are used in combination, the recommended dosage regimens are: AGENERASE 1200 mg with ritonavir 200 mg once daily or AGENERASE 600 mg with ritonavir 100 mg twice daily. Pediatric Patients: For adolescents (13 to 16 years), the recommended oral dose of AGENERASE Capsules is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. For patients between 4 and 12 years of age or for patients 13 to 16 years of age with weight of <50 kg, the recommended oral dose of AGENERASE Capsules is 20 mg/kg twice daily or 15 mg/kg 3 times daily (to a maximum daily dose of 2400 mg) in combination with other antiretroviral agents.
Route of Administration: Oral
The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, 43 H9) and in peripheral blood lymphocytes. The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 mcg/mL).
Substance Class Chemical
Created
by admin
on Sun Dec 18 20:42:32 UTC 2022
Edited
by admin
on Sun Dec 18 20:42:32 UTC 2022
Record UNII
WOU1621EEG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSAMPRENAVIR
HSDB   INN   MI   WHO-DD  
INN  
Official Name English
GW433908
Code English
(3S)-TETRAHYDRO-3-FURYL ((.ALPHA.S)-.ALPHA.-((1R)-1-HYDROXY-2-(N1-ISOBUTYLSULFANILAMIDO)ETHYL)PHENETHYL)CARBAMATE PHOSPHATE (ESTER)
Common Name English
fosamprenavir [INN]
Common Name English
FOSAMPRENAVIR [MI]
Common Name English
GW433908A
Code English
GW-433908
Code English
CARBAMIC ACID, ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-1-(PHENYLMETHYL)-2-(PHOSPHONOOXY)PROPYL)-, C-(3S)-TETRAHYDRO-3-FURANYL) ESTER
Systematic Name English
Fosamprenavir [WHO-DD]
Common Name English
FOSAMPRENAVIR [VANDF]
Common Name English
FOSAMPRENAVIR [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C97366
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
WHO-ATC J05AE07
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
NDF-RT N0000000246
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
LIVERTOX NBK548011
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
WHO-VATC QJ05AE07
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
NDF-RT N0000175889
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
Code System Code Type Description
EPA CompTox
DTXSID2048296
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
DRUG CENTRAL
1240
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
WIKIPEDIA
Fosamprenavir
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
NCI_THESAURUS
C83720
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
CHEBI
82941
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
ChEMBL
CHEMBL1664
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
FDA UNII
WOU1621EEG
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
MERCK INDEX
M5546
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY Merck Index
EVMPD
SUB25386
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
RXCUI
358262
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY RxNorm
CAS
226700-79-4
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
DRUG BANK
DB01319
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
PUBCHEM
131536
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
HSDB
7340
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
INN
8011
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
LACTMED
Fosamprenavir
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
MESH
C426859
Created by admin on Sun Dec 18 20:42:33 UTC 2022 , Edited by admin on Sun Dec 18 20:42:33 UTC 2022
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC