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| Primary information |
|---|
| ID | 10656 |
| Therapeutic ID | Th1139 |
| Protein Name | Certolizumab pegol |
| Sequence | >Th1139_Certolizumab_pegol
EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGWINTYIGEPIYADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGYRSYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA
|
| Molecular Weight | 91000 |
| Chemical Formula | C2115H3252N556O673S16 |
| Isoelectric Point | 6.6 - 7.2 |
| Hydrophobicity | NA |
| Melting point | 61ºC |
| 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 | NA |
| Toxicity | The oral ld50 observed in mice is determined to be of 300 mg/kg.[MSDS] To this date, there have not been reports of overdosage, however, in case of accidental overexposure close monitoring is recommended.[FDA label] Certolizumab pegol does not present mutagenic potential nor presents effects in fertility and reproductive performance. On the other hand, carcinogenicity studies have not been performed.[FDA label] |
| Metabolism | The presence of PEG group in certolizumab pegol delays the metabolism and elimination of this drug. However, once under metabolism, the PEG group gets cleaved from the parent compound and the antibody section is thought to be internalized cells and rescued from metabolism by recycling. Later, it is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] On the other hand, the PEG section is processed normally by the action of the alcohol dehydrogenase to the formation of carboxylic acid.[A176672] |
| Absorption | After subcutaneous administration, the peak plasma concentration is reached between 54 and 171 hours with a bioavailability of 80%.[A176606] Certolizumab presents a linear pharmacokinetic profile with a peak plasma concentration of 43-49 mcg/ml.[F4232] |
| Certolizumab pegol volume of distribution is reported to be in the range of 4-8 L.[A176666] It is known to have a very good distribution in the joints when compared to other TNF-alpha inhibitors.[A176645] |
| Clearance | The clearance rate of certolizumab pegol ranged between 9-14 ml/h when administered intravenously. However, when administered subcutaneously, the clearance rate is estimated to range between 14-21 ml/h depending on the patient condition.[F4232] |
| Categories | TNF inhibitor |
| Patents Number | CA2380298 |
| Date of Issue | 28-09-2010 |
| Date of Expiry | 6-May-2021 |
| Drug Interaction | NA |
| Target | Tumor necrosis factor |
| Brand Name | Cimzia |
| Company | UCB |
| Brand Description | UCB |
| Prescribed For | Crohn's Disease, Rheumatoid Arthritis, Psoriatic Arthritis |
| Chemical Name | NA |
| 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. |
| Physical Appearance | 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 | NA |
| Side Effects | Serious Infections, Malignancies, Heart Failure |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |