You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameRomiplostim
Accession NumberDB05332
TypeBiotech
GroupsApproved
Description

Romiplostim is a thrombopoiesis stimulating dimer Fc-peptide fusion protein (peptibody) to increase platelet production through activation of the thrombopoietin receptor. The peptibody molecule has two identical single-chain subunits, each one is made up of 269 amino acid residues. Each subunit consists of an IgG1 Fc carrier domain that is covalently attached to a polypeptide sequence that contains two binding domains to interact with thrombopoietin receptor c-Mpl. Each domain consists of 14 amino acids. Interestingly, romiplostim’s amino acid sequence is not similar to that of endogenous thrombopoietin. Romiplostim is produced by recombinant DNA technology in Escherichia coli. FDA approved on August 22, 2008.

Protein structureNo structure small
Protein chemical formulaC2634H4086N722O790S18
Protein average weight59 kDa
Sequences
>Thrombopoietin receptor binding domain amino acid sequence 
IEGPTLRQWLAARA
>Amino acid sequence for Fc fusion compound
MDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGIEGPTLR
QWLAARAGGGGGGGGIEGPTLRQWLAARA
Download FASTA Format
Synonyms
SynonymLanguageCode
SemaxanibNot AvailableNot Available
SemaxinibNot AvailableNot Available
SID49674962Not AvailableNot Available
SID50107014Not AvailableNot Available
SU-5416Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
NplateAmgen
Brand mixturesNot Available
Categories
CAS number267639-76-9
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
IndicationTreatment of chronic immune thrombocytopenic purpura.
PharmacodynamicsResponses to platelet increase varies between patients thus indicating a need for individualization of dose. However, a dose dependent-increase in platelet counts have been observed in clinical trials. Does not affect platelet destruction.
Mechanism of actionRomiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c-Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow.
AbsorptionCmax, healthy volunteers, subQ = 24-36 hours; Cmax, immune thrombocytopenia patients, subQ = 7-50 hours (median = 14 hours). Not affected by age, weight, or gender. Accumulation does not occur after six weekly doses of 3 mcg/kg romiplostim.
Volume of distribution

In healthy volunteers, non-linear decrease in Vd with increase IV dose of romiplostim which indicates saturation of c-Mpl receptors.
Vd, 0.3 μg/kg = 122 mL/kg
Vd, 10 μg/kg = 48.2 mL/kg

Protein bindingNot Available
Metabolism
Route of eliminationRenal clearance (more dominant mode of clearance as dose increases) and binding to c-Mpl receptors (dominant mode of clearance at low doses)
Half lifeImmune thrombocytopenia patients, subQ = 3.5 days (median) (range 1-34 days)
ClearanceNot Available
ToxicityThe most common adverse reactions (≥ 5% higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at ≥ 5% higher patient incidence in Nplate versus placebo. LD50 = 980 mg/kg.
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, powder, for solutionSubcutaneous250 mcg
Injection, powder, for solutionSubcutaneous500 mcg
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T, Arai Y, Sonehara Y, Nichol JL: Pharmacodynamics and Pharmacokinetics of AMG 531, a Thrombopoiesis-Stimulating Peptibody, in Healthy Japanese Subjects: A Randomized, Placebo-Controlled Study. J Clin Pharmacol. 2007 Dec;47(12):1489-97. Epub 2007 Oct 9. Pubmed
  2. Rice L: Drug evaluation: AMG-531 for the treatment of thrombocytopenias. Curr Opin Investig Drugs. 2006 Sep;7(9):834-41. Pubmed
  3. Keating GM: Romiplostim: a review of its use in immune thrombocytopenia. Drugs. 2012 Feb 12;72(3):415-35. doi: 10.2165/11208260-000000000-00000. Pubmed
  4. FDA label
  5. http://www.google.com/patents/US6835809
  6. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6835809.PN.&OS=PN/6835809&RS=PN/6835809
External Links
ResourceLink
RxListhttp://www.rxlist.com/nplate-drug.htm
Drugs.comhttp://www.drugs.com/monograph/romiplostim.html
WikipediaRomiplostim
ATC CodesB02BX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(232 KB)
MSDSshow(479 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Thrombopoietin receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Thrombopoietin receptor P40238 Details

References:

  1. Krzyzanski W, Sutjandra L, Perez-Ruixo JJ, Sloey B, Chow AT, Wang YM: Pharmacokinetic and pharmacodynamic modeling of romiplostim in animals. Pharm Res. 2013 Mar;30(3):655-69. doi: 10.1007/s11095-012-0894-2. Epub 2012 Dec 19. Pubmed 23250851

Comments
comments powered by Disqus
Drug created on November 18, 2007 11:23 / Updated on May 08, 2014 12:37