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
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
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 |
DescriptionCurator'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
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23519392 |
8.6 µM [EC50] | ||
Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10952482 |
2.5 µM [IC50] | ||
Target ID: CHEMBL243 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | AGENERASE Approved UseAGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Launch Date1999 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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%) Sources: Page: p.1387Vomiting (6%) Loose stools (3%) Abdominal pain (2%) Abdominal discomfort (2%) Rash (3%) |
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) Sources: Page: p.11Stevens-Johnson syndrome (grade 3-4) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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) Sources: Page: p.1387zidovudine, po(300 mg, BID) |
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
Title | Date | PubMed |
---|---|---|
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 |
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
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admin
on
Edited
Fri Dec 15 16:06:59 GMT 2023
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admin
on
Fri Dec 15 16:06:59 GMT 2023
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Record UNII |
ID1GU2627N
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
TELZIR (AUTHORIZED: HIV INFECTIONS)
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NCI_THESAURUS |
C783
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m5546
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DTXSID0046777
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226700-81-8
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C61771
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100000089666
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402365
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ID1GU2627N
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DBSALT001228
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CHEMBL1664
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131535
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SUB20055
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1283368
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ID1GU2627N
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MM-82
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PARENT -> SALT/SOLVATE | |||
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SOLVATE->ANHYDROUS |
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ACTIVE MOIETY |