Tocilizumab

Các tên gọi khác (3) :

Atlizumab
MRA
RoActemra®

Thuốc Gốc

Biotech

CAS: 375823-41-9

ATC: L04AC07

CTHH: C₆₄₂₈H₉₉₇₆N₁₇₂₀O₂₀₁₈S₄₂

PTK: 148 kDa

Tocilizumab is a recombinant, humanized, anti-human interleukin 6 (IL-6) receptor monoclonal antibody that achieves a significant therapeutic response rate. The light chain is made up of 214 amino acids. The heavy chain is made up of 448 amino acids. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. FDA approved on January 8, 2010.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₆₄₂₈H₉₉₇₆N₁₇₂₀O₂₀₁₈S₄₂

Phân tử khối

148 kDa

Dược Lực Học : A decrease in C-reactive protein (CRP) was noted as early as week 2. Changes in pharmacodynamic parameters were observed (i.e., decreases in rheumatoid factor, erythrocyte sedimentation rate (ESR), serum amyloid A and increases in hemoglobin) with both doses, however the greatest improvements were observed with 8 mg per kg tocilizumab. Similar pharmacodynamic changes were also observed in active polyarticular juvenile idiopathic arthritis and active systemic juvenile idiopathic arthritis patients.

Cơ Chế Tác Dụng : Tocilizumab is a recombinant, humanized, anti-human interleukin 6 (IL-6) receptor monoclonal antibody that achieves a significant therapeutic response rate. The light chain is made up of 214 amino acids. The heavy chain is made up of 448 amino acids. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. FDA approved on January 8, 2010. Interleukin (IL)-6 plays essential roles not only in the immune response, but also in haematopoiesis and the central nervous system. Deregulated production of IL-6 has been found in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (soJIA), Crohn's disease (CD) and systemic lupus erythematosus (SLE). Furthermore, IL-6 activities can explain many symptoms of these diseases. More importantly, serum levels of IL-6 are correlated with disease activity. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors.

Dược Động Học :

▧ Absorption :
When 4 mg/kg of tocilizumab was given every 4 weeks to RA patients, the pharmacokinetic parameters at steady state are as follows: AUC = 13000 ± 5800 mcg∙h/mL; Cmax = 88.3 ± 41.4 mcg/mL. Tocilizumab accumulates following repeated doses. Furthermore, an increased body weight may increase plasma levels of tocilizumab. When a dose of 8 mg/kg of tocilizumab is given to PJIA patients, the pharmacokinetic parameters are as follows: AUC = 29500 ± 8660 mcg∙h/mL; Cmax = 182 ± 37 mcg/mL. When a dose of 8 mg/kg of tocilizumab is given to SJIA patients, the pharmacokinetic parameters are as follows: AUC = 32200 ± 9960 mcg∙h/mL; Cmax = 245 ± 57.2 mcg/mL.
▧ Volume of Distribution :
In rheumatoid arthritis patients the central volume of distribution was 3.5 L and the peripheral volume of distribution was 2.9 L, resulting in a volume of distribution at steady state of 6.4 L. In pediatric patients with PJIA, the central volume of distribution was 1.98 L, the peripheral volume of distribution was 2.1 L, resulting in a volume of distribution at steady state of 4.08 L. In pediatric patients with SJIA, the central volume of distribution was 0.94 L, the peripheral volume of distribution was 1.60 L resulting in a volume of distribution at steady state of 2.54 L.
▧ Route of Elimination :
Following intravenous dosing, tocilizumab undergoes biphasic elimination from the circulation.
▧ Half Life :
The half-life of tocilizumab is concentration-dependent. The concentration-dependent apparent half-life is up to 11 days for 4 mg/kg and up to 13 days for 8 mg/kg every 4 weeks in patients with RA at steady-state. The half-life in children with PJIA is up to 16 days. The half-life in pediatric patients with SJIA is up to 23 days.
▧ Clearance :
The clearance of tocilizumab decreases with increasing dose. At the 10 mg/kg single dose in RA patients, mean clearance was 0.29 ± 0.10 mL/hr/kg. The total clearance of tocilizumab is concentration-dependent and is the sum of the linear clearance and the nonlinear clearance. At low concentrations, concentration-dependent nonlinear clearance is dominant. At high concentrations, linear clearance dominates. The estimated linear clearances for specific patient populations are as follows: RA = 12.5 mL/h; PJIA, pediatric patients = 5.8 mL/h; SJIA, pediatric patients = 7.1 mL/h.

Độc Tính : Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT.

Chỉ Định : Indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). It is also indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) and active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

Tương Tác Thuốc :

Abatacept Avoid combination due to enhanced adverse effects of abatacept.
Dextromethorphan Dextromethorphan is a CYP2D6 and CYP3A4 substrate. Exposure of dextromethorphan decreases following administration of tocilizumab.
Etanercept Avoid combination due to enhanced immunosuppressive effects.
golimumab Avoid combination due to the enhanced immunosuppression by TNF blockers.
Infliximab Avoid combination because enhanced immunosuppression by anti-TNF agents.
Omeprazole Omeprazole is a CYP2C19 and CYP3A4 substrate. Exposure of omeprazole decreases following administration of tocilizumab..
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Simvastatin Simvastatin is a CYP3A4 and OATP1B1 substrate. Exposure of simvastatin decreases following administration of tocilizumab.
Tofacitinib Avoid combination due to the potential increase in tofacitinib related adverse effects.

Liều Lượng & Cách Dùng : Injection, solution, concentrate - Intravenous - 80 mg/4 mL; 200 mg/10 mL; 400 mg/20 mL

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Genentech

Sản phẩm biệt dược : Actemra

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06273

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02596

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50242-137-01

PharmGKB

http://www.pharmgkb.org/drug/PA165292659

Wikipedia

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

RxList

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

Drugs.com

http://www.drugs.com/international/tocilizumab.html

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