FOSAMPRENAVIR SODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H34N3O9PS.2Na
Molecular Weight	629.57
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].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=FZMGUXZZROZJIT-KMIZVRHLSA-L

InChI=1S/C25H36N3O9PS.2Na/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*+1/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	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pregnane X receptor 35 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23519392	Agonist 2678	8.6 µM [EC50]
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10952482	Inhibitor 8297	2.5 µM [IC50]
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Primary		Approved 8429	AGENERASE Approved Use AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Launch Date 1999

C_max

Value	Dose	Analyte	Population
5.36 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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

Value	Dose	Analyte	Population
18.5 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.85 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
1200 mg single, oral Recommended Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10390223 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: https://pubmed.ncbi.nlm.nih.gov/10390223 Page: p.1688	Sources: https://pubmed.ncbi.nlm.nih.gov/10390223 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://pubmed.ncbi.nlm.nih.gov/11192131 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11

Sourcing

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
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
ZINC	ZINC000003809192	http://zinc15.docking.org/substances/ZINC000003809192
eMolecules	877446	https://www.emolecules.com/cgi-bin/more?vid=877446

PubMed

Title	Date	PubMed
Four new antiretroviral medications will soon offer more options to HIV patients.	1998 Jul-Aug	11365545
Principles and practice of HIV-protease inhibitor pharmacoenhancement.	2001 Apr	11737387
Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1--infected patients.	2001 Apr 1	11317074
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection.	2001 Apr 15	11391161
[Determining resistance in HIV therapy. Careful interpretation only].	2001 Apr 2	11373784
Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo.	2001 Dec 15	11700580
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.	2001 Feb	11159797
[Pharmacological study and clinical effect of HIV protease inhibitor amprenavir].	2001 Jan	11233298
Structure-based design of non-peptide HIV protease inhibitors.	2001 Jan-Feb	11347961
Capillary electrophoretic separation of protease inhibitors used in human immunodeficiency virus therapy.	2001 Jul 13	11486877
Amprenavir: new preparation. Another HIV protease inhibitor: no proven advance.	2001 Jun	11718166
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	11491421
Antiretroviral activity and safety of abacavir in combination with selected HIV-1 protease inhibitors in therapy-naive HIV-1-infected adults.	2001 Jun	11491415
Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.	2001 Jun 15	11417878
Effect of reduced-dose amprenavir in combination with lopinavir on plasma levels of amprenavir in patients infected with HIV.	2001 Mar	11318084
Increased turnover of CCR5+ and redistribution of CCR5- CD4 T lymphocytes during primary human immunodeficiency virus type 1 infection.	2001 Mar 1	11181150
Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373.	2001 Mar 1	11181147
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.	2001 Mar 30	11316998
Assessment of active transport of HIV protease inhibitors in various cell lines and the in vitro blood--brain barrier.	2001 Mar 9	11242145
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.	2001 May 5	11393736
New developments in anti-HIV chemotherapy.	2001 Nov	11562282
Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir.	2001 Oct	11591903
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.	2001 Sep	11448730
Effectors of HIV-1 protease peptidolytic activity.	2001 Sep 18	11551211
Amping amprenavir with ritonavir.	2001 Spring	11570075
Central nervous system toxicity and amprenavir oral solution.	2002 Jan	11816252
[Advances in the domain of HIV].	2002 Jan 19	11850992
Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.	2002 Jan 25	11824819
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.	2002 Jul	12116020
Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.	2002 Jul 10	12095381
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	12134255
Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres.	2002 Jul 18	12109915
Sensitive and simultaneous determination of HIV protease inhibitors in rat biological samples by liquid chromatography-mass spectrometry.	2002 Jun	11933027
Fosamprenavir. Vertex Pharmaceuticals/GlaxoSmithKline.	2002 Mar	12054084
Prevalence of the HIV protease mutation N88S causing hypersensitivity to amprenavir.	2002 May 1	11941567
Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity.	2002 May 3	11953467

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).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:26:24 GMT 2023` Edited by `admin` on `Fri Dec 15 16:26:24 GMT 2023`
Record UNII	XSG28FSA0W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FOSAMPRENAVIR SODIUM

Official Name

English

(3S)-Tetrahydro-3-furyl [(αS)-α-[(1R)-1-hydroxy-2-(N1-isobutylsulfanilamido)ethyl]phenethyl]carbamate, disodium phosphate (ester)

Common Name

English

GW 433908A

Code

English

CARBAMIC ACID, ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-1-(PHENYLMETHYL)-2-(PHOSPHONOOXY)PROPYL)-, C-((3S)-TETRAHYDRO-3-FURANYL) ESTER, DISODIUM SALT

Common Name

English

GW-433908A

Code

English

FOSAMPRENAVIR SODIUM [USAN]

Common Name

English

Fosamprenavir sodium [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C783