Tìm theo
Abatacept
Các tên gọi khác (4 ) :
  • CTLA4-Ig
  • CTLA4-IgG4m
  • CTLA4Ig
  • CTLA4IgG4m
antirheumatic agents, immunosuppressive agents
Thuốc Gốc
Biotech
CAS: 332348-12-6
ATC: L04AA24
ĐG : Bristol-Myers Squibb Co. , http://www.bms.com
CTHH: C3498H5458N922O1090S32
PTK: 92.3 kDa (with glycosylation)
Abatacept 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. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C3498H5458N922O1090S32
Phân tử khối
92.3 kDa (with glycosylation)
Dược Lực Học : Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1. The Fc portion of the drug consists of the hinge region, the CH2 domain, and the CH3 domain of IgG1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy.
Cơ Chế Tác Dụng : Abatacept 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. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077). Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis.
Dược Động Học :
▧ Absorption :
When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%.
▧ Volume of Distribution :
* 0.07 L/kg [RA Patients, IV administration] * 0.09 L/kg [Healthy Subjects, IV administration] * 0.11 L/kg [RA patients, subcutaneous administration]
▧ Route of Elimination :
kidney and liver
▧ Half Life :
16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients.
▧ Clearance :
* 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion] * 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions] * 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight.
Độc Tính : Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.
Chỉ Định : For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.
Tương Tác Thuốc :
  • Anakinra Avoid combination due to enhanced adverse effects of abatacept
  • Belimumab Avoid combination due to enhanced adverse effects of belimumab.
  • Certolizumab pegol Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
  • Denosumab Monitor therapy due to enhanced effects of immunosuppressants and the risk of serious infections.
  • Etanercept Avoid combination because of increased adverse effects of Abatacept.
  • golimumab Avoid combination with abatacept due to the increased chance of serious infection.
  • Infliximab The combination shoould be avoided as there have been reports of increased risk of serious infections.
  • Leflunomide Therapy modification should be considered due to enhanced adverse effects of leflunomide, specifically hematologic toxicity.
  • Natalizumab Avoid combination due to enhanced adverse effects of natalizumab and the risk of infections.
  • Pimecrolimus Avoid combination due to enhanced adverse effects of immunosuppressive agents.
  • Rituximab Avoid combination due to enhanced adverse effects of abatacept.
  • Roflumilast Consider therapy modification due to enhanced immunosuppressive action.
  • Sipuleucel-T Monitor therapy due to reduced therapeutic effect of sipuleucel-t.
  • Tacrolimus Avoid combination due to enhanced toxic effects of immunosuppressants.
  • Thalidomide Thalidomide may increase the adverse effects of Abatacept. Increased risk of serious infection. Concomitant therapy should be avoided.
  • Tocilizumab Avoid combination due to enhanced adverse effects of abatacept.
  • Tofacitinib Avoid combination due to the potential increase in tofacitinib related adverse effects.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Intravenous - 250 mg
Injection, solution - Subcutaneous - 125 mg/mL
Dữ Kiện Thương Mại
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Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01281
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03203
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0003-2187-10
PharmGKB
http://www.pharmgkb.org/drug/PA164747080
Wikipedia
http://en.wikipedia.org/wiki/Abatacept
RxList
http://www.rxlist.com/cgi/generic/orencia.htm
Drugs.com
http://www.drugs.com/cdi/abatacept.html
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