Tìm theo
Everolimus
Các tên gọi khác (6 ) :
  • Afinitor
  • Certican
  • RAD001
  • SDZ-RAD
  • VOTUBIA
  • Zortress
Thuốc giảm miễn dịch
Thuốc Gốc
Small Molecule
CAS: 159351-69-6
ATC: L04AA18, L01XE10
ĐG : Chunghwa Chemical Synthesis and Biotech Co. Ltd. , http://www.ccsb.com.tw
CTHH: C53H83NO14
PTK: 958.2244
Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C53H83NO14
Phân tử khối
958.2244
Monoisotopic mass
957.581356369
InChI
InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34+,35-,36-,38-,39-,40+,41+,43+,44-,45?,46+,48+,49-,53-/m0/s1
InChI Key
InChIKey=HKVAMNSJSFKALM-CYUZEOOHSA-N
IUPAC Name
(1S,9R,15R,18R,19R,21S,23R,30S,32R,35S)-1,18-dihydroxy-12-[(2S)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
Traditional IUPAC Name
(1S,9R,15R,18R,19R,21S,23R,30S,32R,35S)-1,18-dihydroxy-12-[(2S)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
SMILES
CO[C@@H]1C[C@H](C[C@H](C)C2CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@@H](C)C[C@@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@H]3CC[C@H](C)[C@](O)(O3)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O2)OC)CC[C@H]1OCCO
Độ hòa tan
1.63e-03 g/l
logP
7.4
logS
-5.8
pKa (strongest acidic)
9.96
pKa (Strongest Basic)
-2.7
PSA
204.66 Å2
Refractivity
261.71 m3·mol-1
Polarizability
105.73 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
13
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Cơ Chế Tác Dụng : Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein. Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake.
Dược Động Học :
▧ Absorption :
In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing. Dose Proportionality in Patients with SEGA (subependymal giant-cell astrocytomas) and TSC (tuberous sclerosis complex): In patients with SEGA and TSC, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m2 to 14.4 mg/m2.
▧ Volume of Distribution :
The blood-to-plasma ratio of everolimus is 17% to 73%.
▧ Protein binding :
~ 74% in both healthy patients and those with moderate hepatic impairment.
▧ Metabolism :
Everolimus is a substrate of CYP3A4 and PgP (phosphoglycolate phosphatase). Three monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus were the 6 primary metabolites detected in human blood. In vitro, everolimus competitively inhibited the metabolism of CYP3A4 and was a mixed inhibitor of the CYP2D6 substrate dextromethorphan.
▧ Route of Elimination :
After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine.
▧ Half Life :
~30 hours.
▧ Clearance :
Following a 3 mg radiolabeled dose of everolimus, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine.
Độc Tính : IC50 of 0.63 nM.
Chỉ Định : Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.
Tương Tác Thuốc :
  • Bicalutamide CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of everolimus. Consider therapy modification. Recommendations regarding optimal management of this interaction vary according to specific indication and product used.
  • Clarithromycin The macrolide, clarithromycin, may increase the serum concentration and toxicity of everolimus.
  • Clotrimazole CYP3A4 Inhibitors (Moderate)such as clotrimazole may increase the serum concentration of everolimus. The prescribing information for the Afinitor branded everolimus product lists indication-specific recommendations for managing this interaction.
  • Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Everolimus prescribing information recommends avoiding concurrent use with strong CYP3A4 inhbitors.
  • Erythromycin The macrolide, erythromycin, may increase the serum concentration and toxicity of everolimus.
  • Etravirine Everolimus, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid this combination. If concurrent therapy cannot be avoided, a gradual dosage increase of everolimus is recommended.
  • Fluconazole Fluconazole may increase everolimus levels/toxicity.
  • Itraconazole Itraconazole may increase everolimus levels/toxicity.
  • Ketoconazole Ketoconazole may increase everolimus levels/toxicity.
  • Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
  • Verapamil Concomitant administration may increase the serum concentrations of both agents. Concurrent use should be avoided.
  • Voriconazole Voriconzole, a strong CYP3A4 inhibitor, may increase the serum concentration of everolimus by decreasing its metabolism. Concurrent therapy should be avoided.
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg
Tablet - Oral - 2.5 mg
Tablet - Oral - 5.0 mg
Tablet - Oral - 7.5 mg
Tablet, for suspension - Oral - 2 mg
Tablet, for suspension - Oral - 3 mg
Tablet, for suspension - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Vesicare 10 mg tablet
    Giá bán buôn : USD >6.98
    Đơn vị tính : tablet
  • Biệt dược thương mại : Vesicare 5 mg tablet
    Giá bán buôn : USD >6.98
    Đơn vị tính : tablet
  • Biệt dược thương mại : Afinitor 5 mg tablet
    Giá bán buôn : USD >234.75
    Đơn vị tính : tablet
  • Biệt dược thương mại : Afinitor 10 mg tablet
    Giá bán buôn : USD >247.58
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Novartis
    Sản phẩm biệt dược : Afinitor
  • Công ty : Novartis
    Sản phẩm biệt dược : Certican
  • Công ty : Novartis
    Sản phẩm biệt dược : VOTUBIA
  • Công ty : Novartis
    Sản phẩm biệt dược : Zortress
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01590
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02714
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0417-20
PharmGKB
http://www.pharmgkb.org/drug/PA164746311
Wikipedia
http://en.wikipedia.org/wiki/Everolimus
RxList
http://www.rxlist.com/afinitor-drug.htm
Drugs.com
http://www.drugs.com/cdi/everolimus.html
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