Belimumab

monoclonal antibodies

Thuốc Gốc

Biotech

CAS: 356547-88-1

CTHH: C ₆₃₅₈ H ₉₉₀₄ N ₁₇₂₈ O ₂₀₁₀ S ₄₄

PTK: 147 kDa

Belimumab is an intravenous immunosupressant for the adjunctive treatment of systemic lupus erythematosus (SLE). More specifically, it is a fully human recombinant IgG1λ monoclonal antibody produced from a recombinant NS0 cell line stably transfected with the belimumab heavy chain and light chain genes. It is the first biological treatment approved for the indication of SLE. Concomitant use with live or inactivated vaccines must be avoided. Belimumab was FDA approved on March 9, 2011. Belimumab consists of 2 heavy chains, and 2 light chains of the lambda subclass. Each heavy chain contains 452 amino acid residues and each light chain contains 214 amino acid residues. There are 3 post-translational modifications: a conserved N-linked glycosylation on the CH2 domain at Asn 303 of the heavy chain, the conversion of the N-terminal glutamine residue of the heavy chain into pyroglutamate, and loss of C-terminal lysine residue of the heavy chain.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C ₆₃₅₈ H ₉₉₀₄ N ₁₇₂₈ O ₂₀₁₀ S ₄₄

Phân tử khối

147 kDa

Dược Lực Học : By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA.

Cơ Chế Tác Dụng : Belimumab is an intravenous immunosupressant for the adjunctive treatment of systemic lupus erythematosus (SLE). More specifically, it is a fully human recombinant IgG1λ monoclonal antibody produced from a recombinant NS0 cell line stably transfected with the belimumab heavy chain and light chain genes. It is the first biological treatment approved for the indication of SLE. Concomitant use with live or inactivated vaccines must be avoided. Belimumab was FDA approved on March 9, 2011. Belimumab consists of 2 heavy chains, and 2 light chains of the lambda subclass. Each heavy chain contains 452 amino acid residues and each light chain contains 214 amino acid residues. There are 3 post-translational modifications: a conserved N-linked glycosylation on the CH2 domain at Asn 303 of the heavy chain, the conversion of the N-terminal glutamine residue of the heavy chain into pyroglutamate, and loss of C-terminal lysine residue of the heavy chain. Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response.

Dược Động Học :

▧ Absorption :
Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-∞), 10 mg/kg, SLE patients = 3083.
▧ Volume of Distribution :
Vdss, 10 mg/kg, SLE patients = 5.29 L.
▧ Metabolism :
Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes.
▧ Half Life :
Terminal elimination half-life, 10 mg/kg, SLE patients= 19.4 days; Distribution half-life, 10 mg/kg, SLE patients = 1.75 days.
▧ Clearance :
Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day.

Độc Tính : The most commonly-reported adverse reactions, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections.

Chỉ Định : Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus.

Tương Tác Thuốc :

Abatacept Avoid combination due to enhanced adverse effects of belimumab.
ado-trastuzumab emtansine Avoid combination due to the increased risk of belimumab associated side effects.
Belatacept Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
Bevacizumab Avoid combination due to enhanced adverse effects of bevacizumab
Cyclophosphamide Avoid combination due to enhanced toxic effects of cyclophosphamide.
Denosumab Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
Etanercept Avoid combination because of enhanced adverse effects of belimumab.
Etanercept Avoid combination due to enhanced toxic effects of belimumab.
Fingolimod Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
Gemtuzumab ozogamicin Avoid combination due to enhanced adverse effects of belimumab.
golimumab Avoid combination with belimumab due to the increased chance of belimumab associated side effects.
Hydroxyurea Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
Ibritumomab Avoid combination due to enhanced adverse effects of belimumab.
Leflunomide Consider modifying therapy as belimumab may enhance the adverse effects of leflunomide, such as hematologic toxicities.
Natalizumab Avoid combination due to enhance adverse effects of natalizumab such as the risk of concurrent infections.
Obinutuzumab Avoid combination due to enhanced toxic effects of monoclonal antibody.
Omalizumab Avoid combination due to enhanced toxic effects of monoclonal antibodies.
Pimecrolimus Avoid combination due to enhanced toxic effects of immunosuppressants.
Roflumilast Consider therapy modification due to enhanced immunosuppressive effect.
Sipuleucel-T Monitor therapy due to decreased therapeutic effect of sipuleucel-t.
Tacrolimus Avoid combination due to enhanced adverse effects of immunosuppressants.
Tofacitinib Avoid combination due to enhanced immunosuppressive effect of tofacitinib.

Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Intravenous - 120 mg, 400 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Human Genome Sciences Inc.

Sản phẩm biệt dược : Benlysta

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB08879

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D03068

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/49401-101-01

Wikipedia

http://en.wikipedia.org/wiki/Belimumab

RxList

http://www.rxlist.com/benlysta-drug.htm

Drugs.com

http://www.drugs.com/ppa/belimumab.html

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