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

Công ty : Bristol Myers Squibb

Sản phẩm biệt dược : Nulojix

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

Bạn thấy hài lòng ?

Bạn chưa hài lòng ?

... loading