Tìm theo
Fosamprenavir
Các tên gọi khác (1) :
  • Fosamprenavir
prodrugs
Thuốc Gốc
Small Molecule
CAS: 226700-79-4
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C25H36N3O9PS
PTK: 585.607
Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C25H36N3O9PS
Phân tử khối
585.607
Monoisotopic mass
585.190986967
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
InChI Key
InChIKey=MLBVMOWEQCZNCC-OEMFJLHTSA-N
IUPAC Name
{[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid
Traditional IUPAC Name
[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxyphosphonic 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
Độ hòa tan
6.85e-01 g/l
logP
1.92
logS
-2.9
pKa (strongest acidic)
1.22
pKa (Strongest Basic)
2.45
PSA
177.72 Å2
Refractivity
144.95 m3·mol-1
Polarizability
57.77 Å3
Rotatable Bond Count
13
H Bond Acceptor Count
8
H Bond Donor Count
4
Physiological Charge
-2
Number of Rings
3
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Fosamprenavir is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. It has little or no antiviral activity until it is hydrolyzed by cellular phosphatases into amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reducing the number of pills required versus standard amprenavir.
Cơ Chế Tác Dụng : Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease. 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.
Dược Động Học :
▧ 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.
▧ 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Abacavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Fosamprenavir. The antiviral response should be closely monitored.
  • Acenocoumarol The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of acenocoumarol.
  • Alprazolam Fosamprenavir may increase the effect and toxicity of the benzodiazepine, alprazolam.
  • Aluminium The antiacid decreases the absorption of amprenavir
  • Amiodarone The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
  • Anisindione The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of anisindione.
  • Astemizole Increased risk of cardiotoxicity and arrhythmias
  • Atorvastatin Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if fosamprenavir is initiated, discontinued or dose changed.
  • Bepridil Amprenavir increases the effect and toxicity of bepridil
  • Bromazepam Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if fosamprenavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
  • Calcium The antiacid decreases the absorption of amprenavir
  • Cisapride Amprenavir increases the effect and toxicity of cisapride
  • Clorazepate Fosamprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.
  • Cyclosporine The protease inhibitor, fosamprenavir, may increase the effect of cyclosporine.
  • Dantrolene Fosamprenavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if fosamprenavir is initiated, discontinued or dose changed.
  • Delavirdine Decreased levels of delavirdine with increased levels of amprenavir
  • Diazepam Fosamprenavir may increase the effect and toxicity of the benzodiazepine, diazepam.
  • Dicoumarol The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of dicumarol.
  • Dihydroergotamine Amprenavir increases the effect and toxicity of ergot derivative
  • Ergotamine Amprenavir increases the effect and toxicity of ergot derivative
  • Etravirine Fosamprenavir, when administered concomitantly with etravirine, may experience an increase in the serum concentration of its active metabolits. It is recommended to avoid this combination.
  • Fentanyl The protease inhibitor, fosamprenavir, may increase the effect and toxicity of fentanyl.
  • Flurazepam Fosamprenavir may increase the effect and toxicity of the benzodiazepine, flurazepam.
  • Fusidic Acid The protease inhibitor, fosamprenavir, may increase the effect and toxicity of fusidic acid.
  • Lovastatin Fosamprenavir, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Lurasidone Concomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
  • Magnesium The antiacid decreases the absorption of amprenavir
  • Magnesium oxide The antiacid decreases the absorption of amprenavir
  • Methadone The protease inhibitor, fosamprenavir, may decrease the effect of methadone.
  • Midazolam Fosamprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Pimozide Amprenavir increases the effect and toxicity of pimozide
  • Ranolazine Increased levels of ranolazine - risk of toxicity
  • Rifabutin Amprenavir increases the effect and toxicity of rifabutin
  • Rifampicin Rifampin may decrease the effectiveness of fosamprenavir.
  • Sildenafil The protease inhibitor, fosamprenavir, may increase the effect and toxicity of sildenafil.
  • Simvastatin Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if fosamprenavir is initiated, discontinued or dose changed.
  • St. John's Wort St. John's Wort decreases the effect of indinavir
  • Tacrolimus The protease inhibitor, Fosamprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Fosamprenavir therapy is initiated, discontinued or altered.
  • Tadalafil Fosamprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Fosmprenavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
  • Tamsulosin Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Fosamprenavir is initiated, discontinued, or dose changed.
  • Telithromycin Fosamprevavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
  • Temsirolimus Fosamprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Fosamprenavir is initiated, discontinued or dose changed.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Tiagabine The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Fosamprenavir is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Fosamprenavir. Consider alternate therapy.
  • Tolterodine Fosamprenavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Tramadol Fosamprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The protease inhibitor, Fosamprenavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Fosamprenavir is initiated, discontinued or dose changed.
  • Triazolam Fosamprenavir may increase the effect and toxicity of the benzodiazepine, triazolam.
  • Trimipramine The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Fosamprenavir is initiated, discontinued or dose changed.
  • Vardenafil Fosamprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
  • Venlafaxine Fosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Fosamprenavir is initiated, discontinued, or dose changed.
  • Verapamil Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Fosamprenavir is initiated, discontinued or dose changed.
  • Vinblastine Fosamprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Fosamprenavir is initiated, discontinued or dose changed.
  • Vincristine Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Fosamprenavir is initiated, discontinued or dose changed.
  • Vinorelbine Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Fosamprenavir is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole may increase the serum concentration of fosamprenavir by decreasing its metabolism. Fosamprenavir may increase the serum concentration of voriconazole. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
  • Warfarin The protease inhibitor, fosamprenavir, may increase the anticoagulant effect of warfarin.
  • Zolpidem Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if fosamprenavir is initiated, discontinued or dose changed.
  • Zonisamide Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if fosamprenavir is initiated, discontinued or dose changed.
  • Zopiclone Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if fosamprenavir is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Suspension - Oral
Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Lexiva 700 mg tablet
    Giá bán buôn : USD >14.78
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Lexiva
  • Công ty :
    Sản phẩm biệt dược : Telzir
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01319
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=131536
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504901
ChemSpider
http://www.chemspider.com/Chemical-Structure.116245.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0721-00
PharmGKB
http://www.pharmgkb.org/drug/PA10084
Wikipedia
http://en.wikipedia.org/wiki/Fosamprenavir
RxList
http://www.rxlist.com/cgi/generic/lexiva.htm
Drugs.com
http://www.drugs.com/cdi/fosamprenavir.html
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