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Identification
NameCertolizumab pegol
Accession NumberDB08904
TypeBiotech
GroupsApproved
Description

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

Protein structureNo structure small
Protein chemical formulaC2115H3252N556O673S16
Protein average weight91 kDa
Sequences
>Amino acid sequence of the light chain
DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASFLYSGVPY
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYNIYPLTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Amino acid sequence of the heavy chain
EVQLVESGGGLVQPGGSLRLSCAASGYVFTDYGMNWVRQAPGKGLEWMGWINTYIGEPIY
ADSVKGRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCARGYRSYAMDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA
Download FASTA Format
Synonyms
SynonymLanguageCode
CDP870Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Cimzia UCB, Inc.
Brand mixturesNot Available
Categories
CAS number428863-50-7
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationReducing signs and symptoms of Crohn's disease and treatment of moderately to severely active rheumatoid arthritis (RA).
PharmacodynamicsTNFα 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 actionCertolizumab 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.
AbsorptionThere 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

Protein bindingNot Available
Metabolism

Metabolism has not been studied in humans.

Route of eliminationThe 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 lifeTerminal 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;

ToxicityThe most common adverse reactions (incidence ≥7% and higher than placebo): upper respiratory tract infection, rash, and urinary tract infection.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous200 mg
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada23802982010-09-282021-06-05
Properties
Statesolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. FDA label
  2. Chimenti MS, Saraceno R, Chiricozzi A, Giunta A, Chimenti S, Perricone R: Profile of certolizumab and its potential in the treatment of psoriatic arthritis. Drug Des Devel Ther. 2013 Apr 15;7:339-48. doi: 10.2147/DDDT.S31658. Print 2013. Pubmed
  3. Ferrante M, Vermeire S, Rutgeerts P: Certolizumab pegol in the treatment of Crohn’s disease. Expert Opin Biol Ther. 2013 Apr;13(4):595-605. doi: 10.1517/14712598.2013.777039. Epub 2013 Mar 4. Pubmed
  4. https://data.epo.org/publication-server/rest/v1.0/publication-dates/20110803/patents/EP1534753NWB1/document.html
External Links
ResourceLink
PharmGKBPA165107055
RxListhttp://www.rxlist.com/cimzia-drug.htm
Drugs.comhttp://www.drugs.com/ppa/certolizumab-pegol.html
WikipediaCertolizumab_pegol
ATC CodesL04AB05
AHFS Codes
  • 56:92
PDB EntriesNot Available
FDA labelshow(595 KB)
MSDSshow(479 KB)
Interactions
Drug Interactions
Drug
AbataceptCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
AnakinraCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
EtanerceptAvoid combination as certolizumab pegol toxic effects would be enhanced.
golimumabAvoid combination due to the potential increased immunosuppression of Certolizumab Pegol.
InfliximabAvoid combination because anti-TNF agents increase adverse effects of certolizumab pegol
NatalizumabCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
RituximabCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
TofacitinibCertolizumab (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.
Food InteractionsNot Available

Targets

1. Tumor necrosis factor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: neutralizer

Components

Name UniProt ID Details
Tumor necrosis factor P01375 Details

References:

  1. FDA label
  2. Chimenti MS, Saraceno R, Chiricozzi A, Giunta A, Chimenti S, Perricone R: Profile of certolizumab and its potential in the treatment of psoriatic arthritis. Drug Des Devel Ther. 2013 Apr 15;7:339-48. doi: 10.2147/DDDT.S31658. Print 2013. Pubmed

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Drug created on June 11, 2013 00:11 / Updated on June 11, 2013 23:57