AMPRENAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H35N3O6S
Molecular Weight	505.627
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

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

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

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pregnane X receptor 36	Agonist 2,752	8.6 µM [EC50]
Cytochrome P450 3A 22	Inhibitor 8,504	2.5 µM [IC50]
Human immunodeficiency virus type 1 protease 36	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156	Primary		Approved 8,583	AGENERASE

C_max

Value	Dose	Analyte	Population
5.36 μg/mL	1200 mg 2 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens
6.18 μg/mL	1200 mg single, oral	AMPRENAVIR plasma	Homo sapiens
9.72 μg/mL	1200 mg single, oral	AMPRENAVIR plasma	Homo sapiens
6.77 μg/mL	20 mg/kg bw 2 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens
3.99 μg/mL	15 mg/kg bw 3 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
18.5 μg × h/mL	1200 mg 2 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens
22.06 μg × h/mL	1200 mg single, oral	AMPRENAVIR plasma	Homo sapiens
28.05 μg × h/mL	1200 mg single, oral	AMPRENAVIR plasma	Homo sapiens
15.46 μg × h/mL	20 mg/kg bw 2 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens
8.73 μg × h/mL	15 mg/kg bw 3 times / day multiple, oral	AMPRENAVIR plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.85 h	1200 mg 2 times / day multiple, oral		AMPRENAVIR plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
10%	1200 mg 2 times / day multiple, oral		AMPRENAVIR plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62	Disc. AE: Nausea, Vomiting...
1200 mg single, oral Recommended	unhealthy, 33+/-6.7
1200 mg 2 times / day multiple, oral Recommended	unhealthy	Disc. AE: Reaction skin, Stevens-Johnson syndrome...

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AEs

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AE	Significance	Dose	Population
Nausea	12% Disc. AE	1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62
Abdominal discomfort	2% Disc. AE	1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62
Abdominal pain	2% Disc. AE	1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62
Loose stools	3% Disc. AE	1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62
Rash	3% Disc. AE	1200 mg 2 times / day multiple, oral Recommended	unhealthy, 21-62

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:40050	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:40050
ChemicalBook	CB4186139	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4186139
eMolecules	877446	https://www.emolecules.com/cgi-bin/more?vid=877446
MolPort	MolPort-000-883-856	https://www.molport.com/shop/molecule-link/MolPort-000-883-856
Selleck Chemicals	Amprenavir-(Agenerase)	http://www.selleckchem.com/products/Amprenavir-(Agenerase).html

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PubMed

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Title	Date	PubMed
Simultaneous determination of the new HIV protease inhibitor lopinavir (ABT 378) and of indinavir(1), amprenavir, saquinavir, ritonavir (ABT 538)(2) and nelfinavir(3) in human plasma by gradient HPLC.	2001	11596909
Early detection of mixed mutations selected by antiretroviral agents in HIV-infected primary human lymphocytes.	2001	11594690
Principles and practice of HIV-protease inhibitor pharmacoenhancement.	2001 Apr	11737387
HIV and drug allergy.	2001 Aug	11964706
Genotypic correlates of resistance to HIV-1 protease inhibitors on longitudinal data: the role of secondary mutations.	2001 Dec	11878405

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Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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).

Show entries

Name

Type

Language

J05AE05

Preferred Name

English

AMPRENAVIR

Official Name

English

AMPRENAVIR [EMA EPAR]

Common Name

English

VX-478

Code

English

AMPRENAVIR [VANDF]

Common Name

English

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Classification Tree

Code System

Code

SEXUALLY TRANSMITTED DISEASES, VIRAL

EMA ASSESSMENT REPORTS

AGENERASE (WITHDRAWN: HIV INFECTIONS)

Protease inhibitors

WHO-ATC

J05AE05

Established Pharmacologic Class

NDF-RT

N0000175889

Anti-HIV Agent

NCI_THESAURUS

C97366

Protease Inhibitors

NDF-RT

N0000000246

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Code System

Code

Type

Description

NDF-RT

N0000182141

PRIMARY

Cytochrome P450 3A4 Inhibitors [MoA]

DAILYMED

5S0W860XNR

PRIMARY

NDF-RT

N0000185506

PRIMARY

Cytochrome P450 3A4 Inducers [MoA]

DRUG CENTRAL

200

PRIMARY

MESH

C095108

PRIMARY

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ACTIVE MOIETY


					5S0W860XNR

AMPRENAVIR

METABOLITE (PARENT)


					65P19KZ7JJ

4-AMINO-N-((2R,3S)-3-AMINO-2-HYDROXY-4-PHENYLBUTYL)-N-(2-METHYLPROPYL)BENZENESULFONAMIDE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound