U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H34N3O9PS.Ca
Molecular Weight 623.669
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSAMPRENAVIR CALCIUM

SMILES

[Ca++].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=PMDQGYMGQKTCSX-HQROKSDRSA-L
InChI=1S/C25H36N3O9PS.Ca/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);/q;+2/p-2/t21-,23-,24+;/m0./s1

HIDE SMILES / InChI

Molecular Formula C25H34N3O9PS
Molecular Weight 583.591
Charge -2
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula Ca
Molecular Weight 40.078
Charge 2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

1999
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
Principles and practice of HIV-protease inhibitor pharmacoenhancement.
2001 Apr
HIV and drug allergy.
2001 Aug
Genotypic correlates of resistance to HIV-1 protease inhibitors on longitudinal data: the role of secondary mutations.
2001 Dec
Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience.
2001 Dec
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.
2001 Dec
Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo.
2001 Dec 15
Amprenavir: new preparation. Another HIV protease inhibitor: no proven advance.
2001 Jun
Resistant to everything.
2001 May
From amprenavir to GW433908.
2001 Nov
Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.
2001 Nov 15
Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients.
2001 Nov 23
In vitro activity of amprenavir against Pneumocystis carinii.
2001 Sep
Retroviral proteases.
2002
Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist.
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
In-vitro and in-vivo pharmacokinetic interactions of amprenavir, an HIV protease inhibitor, with other current HIV protease inhibitors in rats.
2002 Feb
A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site.
2002 Feb
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
Central nervous system toxicity and amprenavir oral solution.
2002 Jan
Clinical pharmacology and pharmacokinetics of amprenavir.
2002 Jan
Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity.
2002 Jan 17
[Advances in the domain of HIV].
2002 Jan 19
Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.
2002 Jan 25
Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir?
2002 Jan 25
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.
2002 Jul
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002 Jul
Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.
2002 Jul 10
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
Determination of lopinavir and nevirapine by high-performance liquid chromatography after solid-phase extraction: application for the assessment of their transplacental passage at delivery.
2002 Jul 15
Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres.
2002 Jul 18
New developments in anti-HIV chemotherapy.
2002 Jul 18
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
Sensitive and simultaneous determination of HIV protease inhibitors in rat biological samples by liquid chromatography-mass spectrometry.
2002 Jun
Fosamprenavir. Vertex Pharmaceuticals/GlaxoSmithKline.
2002 Mar
Lipodystrophy update.
2002 Mar
Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor.
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
The utility of inhibitory quotients in determining the relative potency of protease inhibitors.
2002 Mar 29
Delavirdine increases drug exposure of ritonavir-boosted protease inhibitors.
2002 Mar 29
Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy.
2002 Mar 29
FDA approves new dosing for amprenavir and ritonavir combination.
2002 Mar 8
Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection.
2002 Mar 8
Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.
2002 Mar-Apr
Prevalence of the HIV protease mutation N88S causing hypersensitivity to amprenavir.
2002 May 1
Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity.
2002 May 3
Select HIV protease inhibitors alter bone and fat metabolism ex vivo.
2002 May 31
Therapeutic vaccination in primary HIV infection, the Quest trial.
2002 May 6
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 Fri Dec 15 16:06:59 GMT 2023
Edited
by admin
on Fri Dec 15 16:06:59 GMT 2023
Record UNII
ID1GU2627N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSAMPRENAVIR CALCIUM
EMA EPAR   MART.   ORANGE BOOK   USAN   WHO-DD  
USAN  
Official Name English
(3S)-Tetrahydro-3-furyl [(αS)-α-[(1R)-1-hydroxy-2-(N1-isobutylsulfanilamido)ethyl]phenethyl]carbamate, calcium phosphate (ester) (1:1)
Common Name English
FOSAMPRENAVIR CALCIUM [EMA EPAR]
Common Name English
(3S)-TETRAHYDRO-3-FURYL ((.ALPHA.S)-.ALPHA.-((1R)-1-HYDROXY-2-(N(SUP 1)-ISOBUTYLSULFANILAMIDO)ETHYL)PHENETHYL)CARBAMATE, CALCIUM PHOSPHATE (ESTER) (1:1)
Common Name English
GW-433908G
Code English
TELZIR
Brand Name English
LEXIVA
Brand Name English
GW 433908G
Code English
FOSAMPRENAVIR CALCIUM [MART.]
Common Name English
FOSAMPRENAVIR CALCIUM [ORANGE BOOK]
Common Name English
Fosamprenavir calcium [WHO-DD]
Common Name English
FOSAMPRENAVIR CALCIUM SALT [MI]
Common Name English
FOSAMPRENAVIR CALCIUM [USAN]
Common Name English
CARBAMIC ACID, ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-1-(PHENYLMETHYL)-2-(PHOSPHONOOXY)PROPYL)-, C-((3S)-TETRAHYDRO-3-FURANYL) ESTER, CALCIUM SALT (1:1)
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS TELZIR (AUTHORIZED: HIV INFECTIONS)
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
NCI_THESAURUS C783
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
Code System Code Type Description
MERCK INDEX
m5546
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID0046777
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
CAS
226700-81-8
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
NCI_THESAURUS
C61771
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
SMS_ID
100000089666
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
RXCUI
402365
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY RxNorm
FDA UNII
ID1GU2627N
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
DRUG BANK
DBSALT001228
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL1664
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
PUBCHEM
131535
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
EVMPD
SUB20055
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
RS_ITEM_NUM
1283368
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
DAILYMED
ID1GU2627N
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
USAN
MM-82
Created by admin on Fri Dec 15 16:06:59 GMT 2023 , Edited by admin on Fri Dec 15 16:06:59 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY