Tìm theo
Aflibercept
Các tên gọi khác (3) :
  • VEGF Trap
  • VEGF Trap-Eye
  • Ziv-Aflibercept
Thuốc điều trị ung thư
Thuốc Gốc
Biotech
CAS: 862111-32-8
ATC: S01LA05
CTHH: C4318H6788N1164O1304S32
PTK: 115 KDa (with glycosylation)
Aflibercept is a recombinant fusion protein that comprises of two main components: the vascular endothelial growth factor (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2 which is then fused to the Fc portion of human IgG1. Structurally, Aflibercept is a dimeric glycoprotein with a protein molecular weight of 96.9 kilo Daltons (kDa). It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa. All five putative N-glycosylation sites on each polypeptide chain predicted by the primary sequence can be occupied with carbohydrate and exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the single unsialylated site associated with the Fc domain. Aflibercept, as an ophthalmic agent, is used in the treatment of macular edema following Central Retinal Vein Occlusion (CRVO) and neovascular Age-Related Macular Degeneration (AMD). Ziv-aflibercept, under the brand name Zaltrap, was developed as an injection for treatment of metastatic colorectal cancer. FDA approved in November 18, 2011 and EMA approved in November 2012.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C4318H6788N1164O1304S32
Phân tử khối
115 KDa (with glycosylation)
Độ hòa tan
>100 mg/mL
Dược Lực Học : Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
Cơ Chế Tác Dụng : Aflibercept is a recombinant fusion protein that comprises of two main components: the vascular endothelial growth factor (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2 which is then fused to the Fc portion of human IgG1. Structurally, Aflibercept is a dimeric glycoprotein with a protein molecular weight of 96.9 kilo Daltons (kDa). It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa. All five putative N-glycosylation sites on each polypeptide chain predicted by the primary sequence can be occupied with carbohydrate and exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the single unsialylated site associated with the Fc domain. Aflibercept, as an ophthalmic agent, is used in the treatment of macular edema following Central Retinal Vein Occlusion (CRVO) and neovascular Age-Related Macular Degeneration (AMD). Ziv-aflibercept, under the brand name Zaltrap, was developed as an injection for treatment of metastatic colorectal cancer. FDA approved in November 18, 2011 and EMA approved in November 2012. Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Dược Động Học :
▧ Absorption :
In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
▧ Volume of Distribution :
After intravenous injection of aflibercept, the volume of distribution is 6 L.
▧ Metabolism :
Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
▧ Route of Elimination :
Via kidney and liver
▧ Half Life :
Intravitreal half-life= 7.13 days in humans; Terminal elimination half-life of free aflibercept in plasma was 5 to 6 days after IV injection of 2 - 4 mg/kg dose.
▧ Clearance :
When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
Độc Tính : For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
Chỉ Định : The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Tương Tác Thuốc :
  • Clozapine Avoid combination with systemic aflibercept due to enhanced adverse effects of clozapine, including the risk of agranulocytosis
Liều Lượng & Cách Dùng : Solution - Intraocular - 2 mg/0.05 mL
Solution - Intravenous - 100 mg/4 mL; 200 mg/8 mL
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08885
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09574
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/61755-005-02
Wikipedia
http://en.wikipedia.org/wiki/Aflibercept
RxList
http://www.rxlist.com/eylea-drug.htm
Drugs.com
http://www.drugs.com/mtm/aflibercept-ophthalmic.html
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