| Primary information |
|---|
| ThPP ID | Th1139 |
| Therapeutic Peptide/Protein Name | Certolizumab pegol |
| Sequence | Light chain: DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQ view full sequnce in fasta |
| Functional Classification | IIb |
| Molecular Weight | 91000 |
| Chemical Formula | C2115H3252N556O673S16 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Elimination half life- 14 days |
| Description | Recombinant Fab' antibody fragment against TNF-alpha, which is conjugated to a ~40kDa Polyethylene glycol (PEG2MAL40K) moiety. PEG helps delay drug elimination. 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 (i.e. Excluding the PEG moiety). FDA approved on April 22, 2008. |
| Indication/Disease | Reducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA). |
| Pharmacodynamics | 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). |
| Mechanism of Action | N.A. |
| Toxicity | The most common adverse reactions: upper respiratory tract infection, rash, and urinary tract infection. |
| Metabolism | Metabolism has not been studied in humans. |
| 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 |
| 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; |
| Categories | TNF inhibitor |
| Patents Number | CA2380298 |
| Date of Issue | 29/09/14 |
| Date of Expiry | 06/06/25 |
| Drug Interaction | N.A. |
| Target | Tumor necrosis factor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Cimzia |
| Company | UCB |
| Brand Discription | CIMZIA (certolizumab pegol) is a TNF blocker. CIMZIA is a recombinant, humanized antibody Fab' fragment, with specificity for human tumor necrosis factor alpha (TNFα), conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). The Fab' fragment is manufactured in E. coli and is subsequently subjected to purification and conjugation to PEG2MAL40K, to generate certolizumab pegol. The Fab' fragment is composed of a light chain with 214 amino acids and a heavy chain with 229 amino acids. The molecular weight of certolizumab pegol is approximately 91 kiloDaltons |
| Prescribed for | Crohn's Disease, Rheumatoid Arthritis, Psoriatic Arthritis |
| Chemical Name | N.A. |
| Formulation | Each single-use prefilled syringe of CIMZIA delivers 200 mg in 1 mL of solution with a pH of approximately 4.7 for subcutaneous use. Each 1 mL syringe of CIMZIA contains certolizumab pegol (200 mg), sodium acetate (1.36 mg), sodium chloride (7.31 mg), and Water for Injection, USP. |
| Physcial Appearnce | CIMZIA is supplied as either a sterile, white, lyophilized powder for solution or as a sterile, solution in a single-use prefilled 1 mL glass syringe for subcutaneous injection |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen. |
| Contraindication | N.A. |
| Side Effects | Serious Infections, Malignancies, Heart Failure |
| Useful Link | http://www.rxlist.com/cimzia-drug.htm http://www.cimzia.com/ http://www.drugs.com/cimzia.html |
| PubMed ID | 25651776, 25645901, 25586216, 25555459, 23620660, 23451881 |
| 3-D Structure | Th1139 light Chainor (Download)Th1139 Heavy Chain (View) or (Download) |