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10327 details
Primary information
ID10327
Therapeutic IDTh1046
Protein NameAbciximab
Sequence>Th1046_Abciximab EVQLQQSGTVLARPGASVKMSCEASGYTFTNYWMHWVKQRPGQGLEWIGAIYPGNSDTSYIQKFKGKAKLTAVTSTTSVYMELSSLTNEDSAVYYCTLYDGYYVFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTH
Molecular Weight145651.1
Chemical FormulaC6462H9964N1690O2049S48
Isoelectric Point6.16
Hydrophobicity-0.424
Melting point71
Half-lifeinitial half-life of less than 10 minutes and a second phase half-life of about 30 minutes
DescriptionAbciximab is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules. It also binds to vitronectin (αvβ3) receptor found on platelets and vessel wall endothelial and smooth muscle cells.
Indication/DiseaseAbciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention and in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.
PharmacodynamicsAbciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. A single intravenous bolus dose from 0.15 mg/kg to 0.30 mg/kg produced rapid dose-dependent inhibition of platelet function. After two hours post-injection with a dose of 0.25 - 0.30 mg/kg, 80% of the GPIIb/IIIa receptors were blocked and platelet aggregation was prevented. GPIIb/IIIa is the major surface receptor involved in the final pathway of platelet aggregation. Bleeding time increases to over 30 minutes at the aforementioned doses. To compare, baseline values were five minutes.
Mechanism of ActionAbciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. This binding is thought to involve steric hindrance and/orconformational alterations which block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. By binding to the vitronectin receptor (also known as the αvβ3 integrin), abciximab blocks effects mediated by this integrin which include cell adhesion. Furthermore, abciximab blocks Mac-1 receptor on monocytes and neutrophils thus inhibiting monocyte adhesion.
ToxicityNA
MetabolismMost likely removed by opsonization via the reticuloendothelial system when bound to platelets, or by human antimurine antibody production. Excreted renally.
AbsorptionNA
NA
ClearanceNA
CategoriesAmino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antiplatelet agents, Blood and Blood Forming Organs, Blood Proteins, Globulins, Hematologic Agents, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulins, Immunoproteins, Miscellaneous Therapeutic Agents, Peptide Fragments, Peptides, Platelet Aggregation Inhibitors Excl. Heparin, Proteins, Serum Globulins
Patents NumberCA1341357
Date of Issue7-May-2002
Date of Expiry7-May-2019
Drug InteractionAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided with Ginkgo biloba.
TargetIntegrin beta-3,Integrin alpha-IIb,Low affinity immunoglobulin gamma Fc region receptor III-B,Complement C1r subcomponent,Complement C1q subcomponent subunit A,Complement C1q subcomponent subunit B,Complement C1q subcomponent subunit C,Low affinity immuno
Brand NameReoPro
CompanyEli Lilly and Company, Janssen Pharmaceuticals, Janssen Biotech, Inc.
Brand DescriptionEli Lilly and Company, Janssen Pharmaceuticals, Janssen Biotech, Inc.
Prescribed ForReoPro is used to lessen the chance of heart attack in people who need percutaneous coronary intervention (PCI), a procedure to open blocked arteries of the heart.
Chemical NameNA
FormulationEach single use vial contains 2 mg/mL of Abciximab in a buffered solution (pH 7.2) of 0.01 M sodium phosphate, 0.15 M sodium chloride and 0.001% polysorbate 80 in Water for Injection. No preservatives are added.
Physical Appearance Clear, colorless, Sterile, non-pyrogenic solution
Route of AdministrationIntravenous administartion
Recommended DosageThe recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous Intravenous infusion of 0.125 _g/kg/min (to a maximum of 10 _g/min) for 12 hours.
ContraindicationActive internal bleeding, Recent (within six weeks) gastrointestinal (GI) or genitourinary (GU) bleeding of clinical significance, History of cerebrovascular accident (CVA) within two years, or CVA with a significant residual neurological deficit, Bleeding diathesis; Administration of oral anticoagulants within seven days unless prothrombin time is I 1.2 times control; Thrombocytopenia (< 100,000 cells/pL); Recent (within six weeks) major surgery or trauma; Intracranial neoplasm, arteriovenous malformation, or aneurysm; Severe uncontrolled hypertension; Presumed or documented history of vasculitis; Use of intravenous dextran before percutaneous coronary intervention, or intent to use it during an intervention.
Side EffectsBleeding; blurred vision; confusion; dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly; sweating; unusual tiredness or weakness
Useful Link 1Link
Useful Link 2NA
RemarksNA