[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram].

Abstract

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.

• Authors: A V Mazurov, D V Pevzner, T N Vlasik, M Ia Ruda
• Journal: Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova (Ross Fiziol Zh Im I M Sechenova) Vol. 90 Issue 5 Pg. 586-99 (May 2004) ISSN: 0869-8139 [Print] Russia (Federation)
• Vernacular Title: Antitrombotsitarnye éffekty antagonista glikoproteinov IIb-IIIa monaframa.
• PMID: 15341084 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, English Abstract, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin Fab Fragments
• Platelet Glycoprotein GPIIb-IIIa Complex

Topics

• Antibodies, Monoclonal (administration & dosage, adverse effects, immunology, pharmacokinetics)
• Cell Degranulation (drug effects)
• Dose-Response Relationship, Drug
• Female
• Hemorrhage (chemically induced)
• Humans
• Hypersensitivity (etiology)
• Immunoglobulin Fab Fragments (administration & dosage, adverse effects, immunology)
• Male
• Middle Aged
• Platelet Aggregation (drug effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors, immunology)
• Thrombosis (drug therapy, pathology)