Certolizumab pegol

Các tên gọi khác (1) :

CDP870

tnf inhibitor

Thuốc Gốc

Biotech

CAS: 428863-50-7

ATC: L04AB05

CTHH: C₂₁₁₅H₃₂₅₂N₅₅₆O₆₇₃S₁₆

PTK: 91 kDa

Certolizumab pegol is a recombinant Fab' antibody fragment against tumor necrosis factor alpha which is conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). Polyethylene glycol helps to delay the metabolism and elimination of the drugs. Chemically, the light chain is made up of 214 amino acid residues while the heavy chain is composed of 229 amino acid residues. The molecular mass of the Fab' antibody fragment itself is 47.8 kDa. It is used for the treatment of rheumatoid arthritis and Crohn’s disease. FDA approved on April 22, 2008

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₁₁₅H₃₂₅₂N₅₅₆O₆₇₃S₁₆

Phân tử khối

91 kDa

Dược Lực Học : TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Biological activity associated to TNFα include the upregulation of cellular adhesion molecules and chemokines, upregulation of major histocompatibility complex (MHC) class I and class II molecules, and direct leukocyte activation. TNFα stimulates the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide. After treatment with certolizumab pegol, patients with Crohn's disease demonstrated a decrease in the levels of C-reactive protein (CRP).

Cơ Chế Tác Dụng : Certolizumab pegol is a recombinant Fab' antibody fragment against tumor necrosis factor alpha which is conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). Polyethylene glycol helps to delay the metabolism and elimination of the drugs. Chemically, the light chain is made up of 214 amino acid residues while the heavy chain is composed of 229 amino acid residues. The molecular mass of the Fab' antibody fragment itself is 47.8 kDa. It is used for the treatment of rheumatoid arthritis and Crohn’s disease. FDA approved on April 22, 2008 Certolizumab pegol binds to free and membrane-bound human TNFα with a KD of 90pM and neutralizes its activity. Extent of neutralization is also dose-dependent. It also inhibited the release of lipopolysaccharide-induced IL-1β from monocytes. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes in which elevated levels have been observed in patients with RA and Crohn's. Certolizumab pegol selectively neutralizes TNFα (IC90 of 4 ng/mL for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay). It does not bind to TNF-β. As certolizumab is only a Fab' fragment and thus missing the Fc region, it does not fix complement or cause antibody-dependent cell-mediated cytotoxicity. Furthermore, apoptosis of monocytes or lymphocytes, or neutrophil degranulation have not been observed in vitro.

Dược Động Học :

▧ Absorption :
There is a linear relationship between dose administered and Cmax and AUC. A mean Cmax of approximately 43 to 49 mcg/mL occurred at Week 5 during the initial loading dose period using the recommended dose regimen for the treatment of patients with rheumatoid arthritis (400 mg sc at Weeks 0, 2 and 4 followed by 200 mg every other week). Tmax, SubQ dose = 54 - 171 hours; Bioavailability, SubQ dose = 80% (range of 76% - 88%)
▧ Volume of Distribution :
Vd, steady state, Crohn's and RA patients = 6 - 8 L
▧ Metabolism :
Metabolism has not been studied in humans.
▧ Route of Elimination :
The route of elimination of certolizumab pegol has not been studied in human subjects. Studies in animals indicate that the major route of elimination of the PEG component is via urinary excretion.
▧ Half Life :
Terminal plasma elimation half-life = 14 days (for all doses);
▧ Clearance :
IV dose, healthy subjects = 9.21 mL/h to 14.38 mL/h; SC dose, Crohn's disease patients = 17 mL/h; SC dose, RA patients = 21.0 mL/h;

Độc Tính : The most common adverse reactions (incidence ≥7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection.

Chỉ Định : Reducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA).

Tương Tác Thuốc :

Abatacept Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Anakinra Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Etanercept Avoid combination as certolizumab pegol toxic effects would be enhanced.
golimumab Avoid combination due to the potential increased immunosuppression of Certolizumab Pegol.
Infliximab Avoid combination because anti-TNF agents increase adverse effects of certolizumab pegol
Natalizumab Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Rituximab Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Tofacitinib Certolizumab (and other anti-TNF immunosuppressants), when used in combination with tofacitinib, may increase the risk of added immunosuppression. It is recommended to avoid concurrent therapy.

Liều Lượng & Cách Dùng : Injection - Subcutaneous - 200 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : UCB, Inc.

Sản phẩm biệt dược : Cimzia

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB08904

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D03441

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50474-710-79

PharmGKB

http://www.pharmgkb.org/drug/PA165107055

Wikipedia

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

RxList

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

Drugs.com

http://www.drugs.com/ppa/certolizumab-pegol.html

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