You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
Related Articles
Protein chemical formulaC2115H3252N556O673S16
Protein average weight91000.0 Da
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
CDP870
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CimziakitUCB, Inc.2008-04-202016-04-05Us
Cimziasolution200 mgsubcutaneousUcb Canada Inc2009-08-31Not applicableCanada
Cimziainjection, solution200 mg/mLsubcutaneousUCB, Inc.2009-05-142016-04-05Us
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIG6ADW90R16
CAS number428863-50-7
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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.
Related Articles
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
Injection, solutionsubcutaneous200 mg/mL
Kit
Solutionsubcutaneous200 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2380298 No2010-09-282021-06-05Canada
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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:23620660 ]
  2. 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:23451881 ]
  3. Link [Link]
External Links
ATC CodesL04AB05
AHFS Codes
  • 56:92
PDB EntriesNot Available
FDA labelDownload (595 KB)
MSDSDownload (479 KB)
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Abatacept.
AdalimumabAdalimumab may increase the immunosuppressive activities of Certolizumab pegol.
AnakinraThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Anakinra.
CanakinumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Canakinumab.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Certolizumab pegol.
EtanerceptEtanercept may increase the immunosuppressive activities of Certolizumab pegol.
golimumabgolimumab may increase the immunosuppressive activities of Certolizumab pegol.
InfliximabInfliximab may increase the immunosuppressive activities of Certolizumab pegol.
LeflunomideThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Leflunomide.
LenalidomideLenalidomide may increase the immunosuppressive activities of Certolizumab pegol.
NatalizumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Natalizumab.
PegloticaseThe therapeutic efficacy of Certolizumab pegol can be decreased when used in combination with Pegloticase.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Certolizumab pegol.
PomalidomidePomalidomide may increase the immunosuppressive activities of Certolizumab pegol.
RilonaceptThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Rilonacept.
RituximabRituximab may increase the immunosuppressive activities of Certolizumab pegol.
RoflumilastRoflumilast may increase the immunosuppressive activities of Certolizumab pegol.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Certolizumab pegol.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Certolizumab pegol.
ThalidomideThalidomide may increase the immunosuppressive activities of Certolizumab pegol.
TocilizumabTocilizumab may increase the immunosuppressive activities of Certolizumab pegol.
TofacitinibThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Certolizumab pegol.
VedolizumabThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Vedolizumab.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
neutralizer
General Function:
Tumor necrosis factor receptor binding
Specific Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
Gene Name:
TNF
Uniprot ID:
P01375
Molecular Weight:
25644.15 Da
References
  1. 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:23620660 ]
Comments
comments powered by Disqus
Drug created on June 11, 2013 00:11 / Updated on March 14, 2016 10:05