Fosamprenavir
Identification
- Summary
Fosamprenavir is an antiretroviral agent used for the treatment and postexposure prophylaxis of human immunodeficiency virus (HIV-1) infection.
- Brand Names
- Lexiva, Telzir
- Generic Name
- Fosamprenavir
- DrugBank Accession Number
- DB01319
- Background
Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 585.607
Monoisotopic: 585.190986967 - Chemical Formula
- C25H36N3O9PS
- Synonyms
- FOS-APV
- Fosamprenavir
- External IDs
- GW-433908
- GW433908
Pharmacology
- Indication
Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission. The use of fosamprenavir is pending revision due to a potential association between the drug and myocardial infarction and dyslipidemia in HIV infected adults.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hiv-1 infection •••••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take.
- Mechanism of action
Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.
Target Actions Organism AHuman immunodeficiency virus type 1 protease inhibitorHuman immunodeficiency virus 1 - Absorption
The absolute oral bioavailability of amprenavir after administration of fosamprenavir in humans has not been established. After administration of a single 1,400 mg dose in the fasted state, fosamprenavir oral suspension (50 mg/mL) and fosamprenavir tablets (700 mg) provided similar amprenavir exposures (AUC), however, the Cmax of amprenavir after administration of the suspension formulation was 14.5 % higher compared with the tablet.
- Volume of distribution
Not Available
- Protein binding
Very high (approximately 90%); primarily bound to alpha 1 -acid glycoprotein. Higher amounts of unbound amprenavir present as amprenavir serum concentrations increase.
- Metabolism
In the gut epithelium during absorption, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system.
- Route of elimination
Excretion of unchanged amprenavir in urine and feces is minimal. The renal elimination of unchanged amprenavir represents approximately 1% of the administered dose; therefore, renal impairment is not expected to significantly impact the elimination of amprenavir. Amprenavir, the active metabolite of fosamprenavir, is metabolized in the liver by the cytochrome P450 enzyme system.
- Half-life
The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours.
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Fosamprenavir can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Fosamprenavir. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Fosamprenavir. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Fosamprenavir. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Fosamprenavir. - Food Interactions
- Avoid alcohol. Drug impairs alcohol metabolism.
- Avoid fatty foods.
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Fosamprenavir calcium ID1GU2627N 226700-81-8 PMDQGYMGQKTCSX-HQROKSDRSA-L Fosamprenavir sodium XSG28FSA0W 226700-80-7 FZMGUXZZROZJIT-KMIZVRHLSA-L - Active Moieties
Name Kind UNII CAS InChI Key Amprenavir prodrug 5S0W860XNR 161814-49-9 YMARZQAQMVYCKC-OEMFJLHTSA-N - Product Images
- Brand Name Prescription Products
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fosamprenavir Calcium Tablet, coated 700 mg/1 Oral Sun Pharmaceutical Industries, Inc. 2019-11-28 Not applicable US Fosamprenavir Calcium Tablet, film coated 700 mg/1 Oral Mylan Pharmaceuticals Inc. 2017-09-18 Not applicable US
Categories
- ATC Codes
- J05AE07 — Fosamprenavir
- Drug Categories
- Acids, Acyclic
- Amides
- Amprenavir and Prodrugs
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- HIV Protease Inhibitors
- Hyperglycemia-Associated Agents
- Protease Inhibitors
- Sulfones
- Sulfur Compounds
- Viral Protease Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzenesulfonamides
- Direct Parent
- Aminobenzenesulfonamides
- Alternative Parents
- Phenylbutylamines / Amphetamines and derivatives / Benzenesulfonyl compounds / Phosphoethanolamines / Aniline and substituted anilines / Monoalkyl phosphates / Organosulfonamides / Tetrahydrofurans / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds show 7 more
- Substituents
- Alkyl phosphate / Amine / Aminobenzenesulfonamide / Aminosulfonyl compound / Amphetamine or derivatives / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Benzenesulfonyl group / Carboximidic acid derivative / Dialkyl ether show 24 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- sulfonamide (CHEBI:82941)
- Affected organisms
- Human Immunodeficiency Virus
Chemical Identifiers
- UNII
- WOU1621EEG
- CAS number
- 226700-79-4
- InChI Key
- MLBVMOWEQCZNCC-OEMFJLHTSA-N
- InChI
- InChI=1S/C25H36N3O9PS/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)/t21-,23-,24+/m0/s1
- IUPAC Name
- {[(2R,3S)-1-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid
- SMILES
- CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1
References
- Synthesis Reference
- US6559815
- General References
- Smith KY, Weinberg WG, Dejesus E, Fischl MA, Liao Q, Ross LL, Pakes GE, Pappa KA, Lancaster CT: Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT. AIDS Res Ther. 2008 Mar 28;5:5. doi: 10.1186/1742-6405-5-5. [Article]
- Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS: Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women. HIV Clin Trials. 2007 Nov-Dec;8(6):371-80. [Article]
- Chapman TM, Plosker GL, Perry CM: Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection. Drugs. 2004;64(18):2101-24. [Article]
- Furfine ES, Baker CT, Hale MR, Reynolds DJ, Salisbury JA, Searle AD, Studenberg SD, Todd D, Tung RD, Spaltenstein A: Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob Agents Chemother. 2004 Mar;48(3):791-8. [Article]
- Sension M: Initial therapy for human immunodeficiency virus: broadening the options. HIV Clin Trials. 2004 Mar-Apr;5(2):99-111. [Article]
- Wood R, Arasteh K, Stellbrink HJ, Teofilo E, Raffi F, Pollard RB, Eron J, Yeo J, Millard J, Wire MB, Naderer OJ: Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2004 Jan;48(1):116-23. [Article]
- Falcoz C, Jenkins JM, Bye C, Hardman TC, Kenney KB, Studenberg S, Fuder H, Prince WT: Pharmacokinetics of GW433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol. 2002 Aug;42(8):887-98. [Article]
- Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
- External Links
- Human Metabolome Database
- HMDB0015416
- KEGG Drug
- D02497
- PubChem Compound
- 131536
- PubChem Substance
- 46504901
- ChemSpider
- 116245
- 358262
- ChEBI
- 82941
- ChEMBL
- CHEMBL1664
- ZINC
- ZINC000003941829
- Therapeutic Targets Database
- DAP000707
- PharmGKB
- PA10084
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Fosamprenavir
- FDA label
- Download (374 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Not Available Human Immunodeficiency Virus (HIV) Infections / Proteinuria 1 4 Completed Treatment Chronic Infection With HIV / HCV Coinfection 1 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 2 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections / Hypertriglyceridemias 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- Dept Health Central Pharmacy
- GlaxoSmithKline Inc.
- Physicians Total Care Inc.
- Remedy Repack
- ViiV Healthcare ULC
- Dosage Forms
Form Route Strength Tablet, coated Oral 700 mg/1 Suspension Oral 50 mg/1mL Tablet, film coated Oral 700 mg/1 Suspension Oral 50 MG/ML Suspension Oral 50 mg / mL Tablet Oral 700 mg Tablet, film coated Oral 700 MG - Prices
Unit description Cost Unit Lexiva 700 mg tablet 14.78USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2224738 No 2002-08-27 2016-06-28 Canada CA2231700 No 2005-08-09 2018-03-10 Canada US6436989 Yes 2002-08-20 2018-06-24 US US6514953 Yes 2003-02-04 2020-01-15 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.685 mg/mL ALOGPS logP 0.84 ALOGPS logP 1.92 Chemaxon logS -2.9 ALOGPS pKa (Strongest Acidic) 1.22 Chemaxon pKa (Strongest Basic) 2.45 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 177.72 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 144.95 m3·mol-1 Chemaxon Polarizability 57.53 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.6363 Blood Brain Barrier + 0.5379 Caco-2 permeable + 0.6992 P-glycoprotein substrate Substrate 0.6482 P-glycoprotein inhibitor I Inhibitor 0.7374 P-glycoprotein inhibitor II Non-inhibitor 0.7819 Renal organic cation transporter Non-inhibitor 0.8671 CYP450 2C9 substrate Substrate 0.5877 CYP450 2D6 substrate Substrate 0.6061 CYP450 3A4 substrate Substrate 0.5805 CYP450 1A2 substrate Non-inhibitor 0.7454 CYP450 2C9 inhibitor Non-inhibitor 0.6627 CYP450 2D6 inhibitor Non-inhibitor 0.8835 CYP450 2C19 inhibitor Non-inhibitor 0.6591 CYP450 3A4 inhibitor Non-inhibitor 0.6317 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6969 Ames test Non AMES toxic 0.598 Carcinogenicity Non-carcinogens 0.78 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5018 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9846 hERG inhibition (predictor II) Non-inhibitor 0.8356
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 240.1437914 predictedDarkChem Lite v0.1.0 [M-H]- 219.83711 predictedDeepCCS 1.0 (2019) [M+H]+ 239.9463914 predictedDarkChem Lite v0.1.0 [M+H]+ 221.66199 predictedDeepCCS 1.0 (2019) [M+Na]+ 240.2766914 predictedDarkChem Lite v0.1.0 [M+Na]+ 227.2678 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Aspartic-type endopeptidase activity
- Specific Function
- Not Available
- Gene Name
- pol
- Uniprot ID
- Q72874
- Uniprot Name
- Pol polyprotein
- Molecular Weight
- 10778.7 Da
References
- Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS: Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women. HIV Clin Trials. 2007 Nov-Dec;8(6):371-80. [Article]
- Furfine ES, Baker CT, Hale MR, Reynolds DJ, Salisbury JA, Searle AD, Studenberg SD, Todd D, Tung RD, Spaltenstein A: Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob Agents Chemother. 2004 Mar;48(3):791-8. [Article]
- Sension M: Initial therapy for human immunodeficiency virus: broadening the options. HIV Clin Trials. 2004 Mar-Apr;5(2):99-111. [Article]
- Wood R, Arasteh K, Stellbrink HJ, Teofilo E, Raffi F, Pollard RB, Eron J, Yeo J, Millard J, Wire MB, Naderer OJ: Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2004 Jan;48(1):116-23. [Article]
- Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
- Hester EK, Chandler HV, Sims KM: Fosamprenavir: drug development for adherence. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1301-10. doi: 10.1345/aph.1G034. Epub 2006 Jun 6. [Article]
- FDA Approved Drug Products: Colcrys (colchicine) tablets for oral use (May 2020) [Link]
- Amprenavir FDA label [Link]
Drug created at June 30, 2007 17:17 / Updated at February 20, 2024 23:54