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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H35N3O6S
Molecular Weight 505.6289
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMPRENAVIR

SMILES

CC(C)CN(C[C@]([H])([C@]([H])(Cc1ccccc1)N=C(O)O[C@@]2([H])CCOC2)O)S(=O)(=O)c3ccc(cc3)N

InChI

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

HIDE SMILES / InChI

Molecular Formula C25H35N3O6S
Molecular Weight 505.6289
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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

924048000000
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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:
1200 mg single, oral
Recommended
Dose: 1200 mg
Route: oral
Route: single
Dose: 1200 mg
Sources:
unhealthy, 33+/-6.7
Health Status: unhealthy
Age Group: 33+/-6.7
Sex: M+F
Sources:
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:
unhealthy
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:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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
Sources:
unhealthy, 21-62
Health Status: unhealthy
Age Group: 21-62
Sex: M+F
Sources:
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:
unhealthy
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:
unhealthy
PubMed

PubMed

TitleDatePubMed
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
BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.
2000 Aug
Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.
2000 Jun 5
2',6'-Dimethylphenoxyacetyl: a new achiral high affinity P(3)-P(2) ligand for peptidomimetic-based HIV protease inhibitors.
2000 Mar 23
A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir.
2000 May
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
Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1--infected patients.
2001 Apr 1
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.
2001 Apr 15
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
Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience.
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
[Pharmacological study and clinical effect of HIV protease inhibitor amprenavir].
2001 Jan
New developments in anti-HIV chemotherapy.
2001 Jan-Feb
Structure-based design of non-peptide HIV protease inhibitors.
2001 Jan-Feb
Effect of reduced-dose amprenavir in combination with lopinavir on plasma levels of amprenavir in patients infected with HIV.
2001 Mar
Phase III trials for new PI.
2001 Mar
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.
2001 Mar 30
Assessment of active transport of HIV protease inhibitors in various cell lines and the in vitro blood--brain barrier.
2001 Mar 9
[Simultaneous quantitative determination of amprenavir and indinavir in human plasma by high-performance liquid chromatography].
2001 Mar-Apr
Drifting agenda for federal treatment research.
2001 May
Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors.
2001 May
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
Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir.
2001 Oct
In vitro activity of amprenavir against Pneumocystis carinii.
2001 Sep
Effectors of HIV-1 protease peptidolytic activity.
2001 Sep 18
Amping amprenavir with ritonavir.
2001 Spring
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
Clinical pharmacology and pharmacokinetics of amprenavir.
2002 Jan
Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity.
2002 Jan 17
Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.
2002 Jan 25
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.
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
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
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
Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection.
2002 Mar 8
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
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 Jun 25 23:24:32 UTC 2021
Edited
by admin
on Fri Jun 25 23:24:32 UTC 2021
Record UNII
5S0W860XNR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMPRENAVIR
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
AMPRENAVIR [EMA EPAR]
Common Name English
VX-478
Code English
AMPRENAVIR [VANDF]
Common Name English
AMPRENAVIR [MART.]
Common Name English
KVX-478
Code English
(3S-(3R*(1R*,2S*)))-(3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL) TETRAHYDRO-3-FURANYL CARBAMATE
Common Name English
AMPRENAVIR [MI]
Common Name English
AMPRENAVIR [HSDB]
Common Name English
AMPRENAVIR [WHO-DD]
Common Name English
141 W94
Code English
AMPRENAVIR [ORANGE BOOK]
Common Name English
J05AE05
Code English
AMPRENAVIR [USAN]
Common Name English
AGENERASE
Brand Name English
AMPRENAVIR [JAN]
Common Name English
AMPRENAVIR [INN]
Common Name English
141W94
Code English
(3S)-TETRAHYDRO-3-FURYL ((.ALPHA.S)-.ALPHA.-((1R-1-HYDROXY-2-(N1-ISOBUTYLSULFANILAMIDO)ETHYL)PHENETHYL)CARBAMATE
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS AGENERASE (WITHDRAWN: HIV INFECTIONS)
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
WHO-ATC J05AE05
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
NDF-RT N0000175889
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
NCI_THESAURUS C97366
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
NDF-RT N0000000246
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
WHO-VATC QJ05AE05
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
LIVERTOX 53
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
Code System Code Type Description
NDF-RT
N0000182141
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000185506
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
DRUG CENTRAL
200
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
MESH
C095108
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
RXCUI
228656
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY RxNorm
PUBCHEM
65016
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
NCI_THESAURUS
C28824
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
INN
7751
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
EPA CompTox
161814-49-9
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
DRUG BANK
DB00701
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
ChEMBL
CHEMBL116
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
WIKIPEDIA
AMPRENAVIR
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
FDA UNII
5S0W860XNR
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
MERCK INDEX
M1855
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000191264
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY P-Glycoprotein Inducers [MoA]
CAS
161814-49-9
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
EVMPD
SUB00511MIG
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
HSDB
7157
Created by admin on Fri Jun 25 23:24:33 UTC 2021 , Edited by admin on Fri Jun 25 23:24:33 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
The high affinity binding protein for amprenavir is alpha1-acid glycoprotein (AAG).
BINDING
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
EXCRETED UNCHANGED
URINE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC