Tìm theo
Belatacept
Các tên gọi khác (6 ) :
  • BMS-224818
  • BMS224818
  • CD152 antigen
  • CTLA4-Ig
  • LEA 29Y
  • LEA29Y
antirheumatic agents, immunosuppressive agents
Thuốc Gốc
Biotech
CAS: 706808-37-9
ATC: L04AA28
CTHH: C3508H5440N922O1096S32
PTK: 92.3 kDa (with glycosylation)
Belatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It is approved for the treatment of rheumatoid arthritis. Belatacept selectively blocks the process of T-cell activation. It was developed by Bristol-Myers-Squibb. It differs from abatacept (Orencia) by only 2 amino acids. FDA approved on June 15, 2011.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C3508H5440N922O1096S32
Phân tử khối
92.3 kDa (with glycosylation)
Dược Lực Học : Belatacept binds to CD86 with a 4-fold higher affinity than abatacept. It also binds to CD80 with a 2-fold higher affinity than abatacept. It was observed in non-human primates that belatacept prolongs graft survival due to a decrease in antibody production against the donor organ. Furthermore, belatacept also inhibits the primary humoral immune response which is indicated by the decrease in post-transplant levels of IgG, IgM, and IgA. The magnitude of this effect is more significant in belatacept than it is in cyclosporine.
Cơ Chế Tác Dụng : Belatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It is approved for the treatment of rheumatoid arthritis. Belatacept selectively blocks the process of T-cell activation. It was developed by Bristol-Myers-Squibb. It differs from abatacept (Orencia) by only 2 amino acids. FDA approved on June 15, 2011. Belatacept is a fusion protein in which the Fc portion of human IgG1 is attached onto the extracellular portion of human CTLA-4 (CD152). Belatacept specifically binds to CD80 and CD86 receptors that are found on the antigen-presenting cell (B cells, macrophages, dendritic cells) to block selective T-cell lymphocyte costimulation. CD80 and CD86 would normally act as the ligands to the CD28 receptor T-cells in which this interaction triggers the activation of T lymphocytes. However in the presence of belatacept, because the extracellular CTLA-4 component binds to CD28 with higher affinity than CD80 or CD86, T lymphyocyte anergy, a state of antigen specific tolerance, occurs instead. The T cell is also no longer able to respond to their antigen.
Dược Động Học :
▧ Absorption :
Following multiple intravenous doses of an initial 10 mg/kg dose and followed by a maintenance dose of 5 mg/kg in kidney transplant recipients, these are the following pharmacokinetic parameters: Cmax, 10 mg/kg = 247 µg/mL; Cmax, 5 mg/kg = 139 µg/mL; AUC, 10 mg/kg = 22,252 µg · h/mL; AUC, 5 mg/kg = 14,090 µg · h/mL; Belatacept had linear and dose-dependent pharmacokinetic profile.
▧ Volume of Distribution :
Vd, steady state, transplant patients, 10 mg/kg = 0.11 L/kg; Vd, steady state, transplant patients, 5 mg/kg = 0.12 L/kg
▧ Metabolism :
The cytochrome P450 enzyme system or uridine diphosphate-glucuronosyltransferases are not expected to be involved with the metabolism of belatacept. Because the drug is a protein, belatacept is degraded into smaller peptides and amino acids by proteolytic enzymes.
▧ Half Life :
Mean terminal elimination half-life: 10 mg/kg, kidney transplant recipients= 9.8 days; 5 mg/kg, kidney transplant recipient = 8.2 days
▧ Clearance :
Increased body weight may increase the clearance rate of belatacept. Mean systemic clearance: 10 mg/kg, kidney transplant recipients= 0.49 mL/h/kg; 5 mg/kg, kidney transplant recipient = 0.51 mL/h/kg.
Chỉ Định : For prophylaxis of organ rejection. It is also used concomitantly with basiliximumab for induction therapy, mycophenolate, and corticosteriods in kidney transplant recepients that are seropositive for the Epstein-Barr virus.
Tương Tác Thuốc :
  • Belimumab Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
  • Denosumab Montinor therapy due to enhanced adverse effects of immunosuppressants and the risk of infections.
  • Leflunomide Consider therapy modification due to enhanced adverse effects of leflunomide, especially hematologic toxicities.
  • Mycophenolate mofetil Belatacept increases the Cmax and AUC of mycophenolate mofetil.
  • Natalizumab Avoid infection due to enhanced adverse effects of natalizumab and the risk of infections.
  • Pimecrolimus Avoid combination due to enhanced effects of immunosuppressants.
  • Pralatrexate Increased immunosuppresive effects and risk of infection. Monitor for adverse effects .
  • Rilonacept Belatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
  • Rilonacept Belatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
  • Rilonacept Belatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
  • Roflumilast Consider modifying therapy due to enhanced immunosuppressive effect.
  • Sipuleucel-T Monitor therapy due to to potential decrease in therapeutic effect of sipuleucel-t.
  • Tacrolimus Avoid combination due to enhanced immunosuppressive effect.
  • Tofacitinib Avoid combination due to enhanced immunosuppressive effect of tofacitinib.
  • Trastuzumab Monitor therapy due to enhanced neutropenic effect of immunosuppressants.
Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Intravenous - 250 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06681
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03222
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0003-0371-13
Wikipedia
http://en.wikipedia.org/wiki/Belatacept
RxList
http://www.rxlist.com/nulojix-drug.htm
Drugs.com
http://www.drugs.com/cdi/belatacept.html
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