Chemical Property of Fosamprenavir Calcium Salt
Chemical Property:
- Appearance/Colour:white microcrystalline needles
- Melting Point:282-284 °C
- PSA：201.57000
- LogP:5.44910
- Storage Temp.:-20°C Freezer, Under Inert Atmosphere
- Solubility.:Aqueous Acid (Slightly), DMF (Slightly)
- Hydrogen Bond Donor Count:4
- Hydrogen Bond Acceptor Count:11
- Rotatable Bond Count:14
- Exact Mass:625.1535788
- Heavy Atom Count:40
- Complexity:912
- Purity/Quality:
-
99% *data from raw suppliers
Fosamprenavir Calcium Salt *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
- Canonical SMILES:CC(C)CN(CC(C(CC1=CC=CC=C1)NC(=O)OC2CCOC2)OP(=O)(O)O)S(=O)(=O)C3=CC=C(C=C3)N.[Ca]
- Isomeric SMILES:CC(C)CN(C[C@H]([C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)OP(=O)(O)O)S(=O)(=O)C3=CC=C(C=C3)N.[Ca]
- Recent EU Clinical Trials:Impact of stomach motility on the gastrointestinal behavior of fosamprenavir in healthy volunteers
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Description
Fosamprenavir, a prodrug of the HIV protease inhibitor amprenavir, is indicated for the
oral treatment of HIV infection in adults in combination with other antiretroviral agents.
Although amprenavir has excellent antiviral potency and good tolerability, its watersolubility
is poor (0.04 mg/ml). As a result, the formulation of the agent includes a high
percentage of organic excipients to facilitate gastric dissolution, which limits the amount
of active drug that can be formulated per capsule. Fosamprenavir is a highly soluble
phosphate ester of amprenavir. It allows more convenient dosing and reduction in pill
counts as compared to amprenavir. Fosamprenavir is readily prepared in two steps
starting from a key intermediate used in the synthesis of amprenavir, by phosphorylating
a hydroxyl group and subsequently reducing a p-nitrophenyl to a p-aminophenyl group.
Fosamprenavir has little or no antiviral activity in vitro. After oral administration, it is
rapidly and almost completely hydrolyzed by phosphatases in the gut epithelium to
amprenavir prior to reaching systemic circulation. The time to reach peak plasma
concentration of amprenavir is approximately 2.5 h and the plasma elimination half-life
is approximately 7.7 h. Amprenavir is metabolized in the liver by CYP3A4 and ＞90% of
the dose is excreted as metabolites in urine and feces. In most patients, fosamprenavir is
administered at daily doses of 700–1400 mg in conjunction with ritonavir. Monotherapy
with fosamprenavir is only recommended in antiretroviral therapy-na?ve patients and the
dosing regimen is 1400 mg twice daily. The most common adverse events experienced
with fosamprenavir are diarrhea, nausea, vomiting, headache and rash. Fosamprenavir (calcium salt) is an orally bioavailable prodrug of the HIV-1 protease inhibitor amprenavir . Fosamprenavir has improved solubility compared with amprenavir, and its pharmacokinetics, either during fasting or with a low- or high-fat meal, suggest that it could be effective using fewer tablets and a less complex dosing schedule than other HIV treatments. Formulations containing fosamprenavir are used for adult and pediatric patients with HIV infection, especially as an initial antiretroviral therapy.
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Uses
HIV protease inhibitor; water soluble prodrug of amprenavir HIV protease inhibitor; water soluble prodrug of amprenavir.
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Clinical Use
Fosamprenavir calcium has been approved for the treatment of HIV in adults when used in combination
with other anti-HIV drugs. It is a prodrug that, on hydrolysis by serum phosphatases, gives rise to
amprenavir, which is a peptidomimetic transition-state inhibitor that targets HIV-1 protease and reduces
the viral replication and, thus, the infectiousness of HIV-1. It is commonly administered in combination
with RT inhibitors to produce excellent efficacy in patients with AIDS. The drug is administered as two
700 mg tablets twice daily or, in combination with ritonavir, can be given as two 700 mg tables once daily
or one 700 mg tablet twice daily. As a result, formaprenavir lowers the "pill burden" in patients with AIDS.
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Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: possibly increased concentration
of amiodarone, flecainide, lidocaine and propafenone
(increased risk of ventricular arrhythmias) - avoid.
Antibacterials: increases concentration of rifabutin
- reduce rifabutin dose; concentration significantly
reduced by rifampicin - avoid; avoid with
telithromycin in severe renal and hepatic impairment.
Anticoagulants: avoid with apixaban and
rivaroxaban.
Antidepressants: concentration reduced by St John’s
wort - avoid.
Antimalarials: use artemether/lumefantrine with
caution; possibly increases quinine concentration.
Antipsychotics: possibly inhibits aripiprazole
metabolism - reduce aripiprazole dose; possibly
increases quetiapine concentration - avoid; possibly
increases pimozide concentration (increased risk of
ventricular arrhythmias) - avoid.
Antivirals: avoid with boceprevir, raltegravir and
telaprevir; concentration of dolutegravir reduced;
concentration increased by etravirine, consider
reducing fosamprenavir dose; concentration
reduced by lopinavir, maraviroc and tipranavir,
effect on lopinavir unpredictable - avoid, avoid
with maraviroc; concentration possibly reduced by
nevirapine; avoid with raltegravir.
Anxiolytics and hypnotics: increased risk of
prolonged sedation and respiratory depression with
midazolam - avoid with oral midazolam.
Avanafil: concentration of avanafil possibly increased.
Cytotoxics: possibly increases concentration of
bosutinib and ibrutinib, avoid or consider reducing
bosutinib and ibrutinib dose.
Ergot alkaloids: increased risk of ergotism - avoid.
Immunosuppressants: monitor ciclosporin,
tacrolimus and sirolimus levels.
Lomitapide: avoid concomitant use.
Orlistat: absorption possibly reduced by orlistat.
Ranolazine: possibly increases ranolazine
concentration - avoid.
Statins: possibly increased risk of myopathy with
atorvastatin; possibly increased myopathy with
simvastatin and rosuvastatin - avoid.
