Tìm theo
Darunavir
Các tên gọi khác (11 ) :
  • (3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamate
  • (3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate
  • (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • [(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • {(1S,2R)-3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • Darunavir
  • Darunavirum
  • N-((1S,2R)-3-(((4-Aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide
  • TMC-114
  • TMC114
hiv protease inhibitors
Thuốc Gốc
Small Molecule
CAS: 206361-99-1
ATC: J05AE10
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C27H37N3O7S
PTK: 547.664
Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C27H37N3O7S
Phân tử khối
547.664
Monoisotopic mass
547.235221243
InChI
InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1
InChI Key
InChIKey=CJBJHOAVZSMMDJ-HEXNFIEUSA-N
IUPAC Name
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1-phenylbutan-2-yl]carbamate
Traditional IUPAC Name
darunavir
SMILES
[H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1
Độ hòa tan
Approximately 0.15 mg/mL at 20 °C as ethanolate salt
logP
1.8
logS
-3.9
pKa (strongest acidic)
13.59
pKa (Strongest Basic)
2.39
PSA
140.42 Å2
Refractivity
142.34 m3·mol-1
Polarizability
57.24 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
7
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir.
Cơ Chế Tác Dụng : Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments. Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme's active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Structual analyses suggests that the close contact that darunavir has with the main chains of the protease active site amino acids (Asp-29 and Asp-30) is an important contributing factor to its potency and wide spectrum of activity against multi-protease inhibitor resistant HIV-1 variants. Darunavir can also adapt to the changing shape of a protease enzyme because of its molecular flexibility. Darunavir is known to bind to two distinct sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer.
Dược Động Học :
▧ Absorption :
The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.
▧ Protein binding :
Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).
▧ Metabolism :
Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.
▧ Route of Elimination :
Darunavir is primarily metabolized by CYP3A. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A. A mass balance study in healthy volunteers showed that after single dose administration of 400 mg 14C-darunavir, co-administered with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of 14C-darunavir was recovered in the feces and urine, respectively.
▧ Half Life :
The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.
▧ Clearance :
* 32.8 L/hr [Healthy volunteers receiving intravenous administration of 400 mg of darunavir] * 5.9 L/hr [Healthy volunteers receiving intravenous administrations of 400 mg of darunavir and 100 mg of ritonavir twice daily]
Chỉ Định : Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.
Tương Tác Thuốc :
  • Abacavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Darunavir. The antiviral response should be closely monitored.
  • Bromazepam Darunavir, 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 darunavir is initiated, discontinued or dose changed. Dosage adjustments may be required.
  • Clarithromycin Increased levels of clarithromycin
  • Dantrolene Darunavir 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 darunavir is initiated, discontinued or dose changed.
  • Etravirine Etravirine, when used concomitantly with protease inhibitors, may experience a decrease in serum concentration. Protease inhibitors, when used concomitantly with etravirine, may experience an increase in serum concentration. Ritonavir boosting of etravirine therapy is a requirement to concurrent therapy. In addition, it is recommended to monitor serum concentrations of the antiretrovirals, as well as to monitor antiretroviral therapy for efficacy.
  • Lidocaine Possible increase in lidocaine levels
  • Lopinavir Decreased levels of darunavir
  • Lovastatin Darunavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
  • Lurasidone Concomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
  • Saquinavir Decreased levels of darunavir
  • Tacrolimus The protease inhibitor, Darunavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Darunavir therapy is initiated, discontinued or altered.
  • Tadalafil Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Darunavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
  • Tamsulosin Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darunavir is initiated, discontinued, or dose changed.
  • Telithromycin Co-administration may result in altered plasma concentrations of Darunavir and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
  • Temsirolimus Darunavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Tiagabine The strong CYP3A4 inhibitor, Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Tolterodine Darunavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The p-glycoprotein inhibitor, Darunavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Tramadol Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The protease inhibitor, Darunavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Darunavir is initiated, discontinued or dose changed.
  • Trimipramine The strong CYP3A4 inhibitor, Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Vardenafil Darunavir, 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 Darunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Darunavir is initiated, discontinued, or dose changed.
  • Verapamil Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Vinblastine Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Vincristine Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Vinorelbine Darunavir, 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 Darunavir is initiated, discontinued or dose changed.
  • Voriconazole Darunavir may reduce serum concentrations and efficacy of voriconazole. This combination should be avoided unless the potential benefits outweigh the risk of reduced voriconazole efficacy.
  • Zolpidem Darunavir, 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 darunavir is initiated, discontinued or dose changed.
  • Zonisamide Darunavir, 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 darunavir is initiated, discontinued or dose changed.
  • Zopiclone Darunavir, 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 darunavir is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Prezista 75 mg tablet
    Giá bán buôn : USD >2.3
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prezista 150 mg tablet
    Giá bán buôn : USD >4.59
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prezista 300 mg tablet
    Giá bán buôn : USD >16.2
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prezista 400 mg tablet
    Giá bán buôn : USD >18.74
    Đơn vị tính : tablet
  • Biệt dược thương mại : Prezista 600 mg tablet
    Giá bán buôn : USD >25.75
    Đơn vị tính : tablet
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01264
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=213039
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506908
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03656
ChemSpider
http://www.chemspider.com/Chemical-Structure.184733.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=8125
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/59676-563-01
PharmGKB
http://www.pharmgkb.org/drug/PA163522472
Wikipedia
http://en.wikipedia.org/wiki/Darunavir
RxList
http://www.rxlist.com/cgi/generic/prezista.htm
Drugs.com
http://www.drugs.com/cdi/darunavir.html
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