[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram].
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%.
Mazurov
A V
AV
Pevzner
D V
DV
Vlasik
T N
TN
Ruda
M Ia
MIa
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000276:immunology; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex