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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
MOL RATIO 1 MOL RATIO (average)
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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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 TargetPharmacologyConditionPotency
8.6 µM [EC50]
2.5 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AGENERASE

Cmax

ValueDoseCo-administeredAnalytePopulation
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

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
8.85 h
1200 mg 2 times / day multiple, oral
AMPRENAVIR plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
1200 mg 2 times / day multiple, oral
AMPRENAVIR plasma
Homo sapiens

Doses

AEs

PubMed

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).
Substance Class Chemical
Record UNII
ID1GU2627N
Record Status Validated (UNII)
Record Version