[Pharmacodynamics, safety, and clinical effects of a novel glycoprotein IIb/IIIa antagonist framon during high risk coronary angioplasty].
Preparation framon [F(ab')2 fragments of the anti-glycoprotein (GP) IIb/IIIa monoclonal antibody (FRaMon)] blocks fibrinogen binding to GP IIb/IIIa and platelet aggregation. Dynamics of platelet aggregation inhibition, safety, and clinical effects of framon were studied in high-risk coronary angioplasty. Twenty seven patients underwent angioplasty with framon, 29 - with abciximab and 28 - with no GP IIb/IIIa antagonists. Framon at 0.2 mg/kg (n=16) and 0.25 mg/kg (n=11) bolus administration inhibited platelet aggregation induced by 20 mcM ADP by more than 90%, 80%, 60% and 30% in comparison with the predrug level 1, 12, 24 and 72 h after injection, respectively. Almost the same dynamics of aggregation inhibition was observed upon abciximab administration at 0.25 mg/kg bolus + 0.125 mcg/kg/min infusion for 12 h. No signs of individual intolerance and side effects including allergic reactions and bleedings were detected in patients treated with framon. Slight decrease of platelet count (15-20%) was observed on the first day after framon administration. Antibodies against framon were detected in 1 out of 22 tested patients. Free (nonbound to platelets) framon was completely removed from the circulation 12 h after injection. The number of endpoints (death, myocardial infarction and indications for repeat revascularization) within 1 year after angioplasty was approximately the same in the groups with framon and abciximab - 7 of 25 (28%) and 7 of 28 (25%), respectively, and more than 1.5 fold higher in the group without GP IIb/IIIa blockers - 12 of 27 (44,4%).
Mazurov
A V
AV
Pevzner
D V
DV
Semenov
A V
AV
Antonova
O A
OA
Dudnik
O A
OA
Khaspekova
S G
SG
Vlasik
T N
TN
Samko
A N
AN
Staroverov
I I
II
Ruda
M Ia
MIa
D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D003131:Combined Modality Therapy; D005260:Female; D005340:Fibrinogen / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D039661:Integrin beta3 / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000601:surgery*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D040201:Platelet Membrane Glycoprotein IIb / Q000187:drug effects*; D011971:Receptors, Immunologic / Q000627:therapeutic use; D012307:Risk Factors
C052643:F(ab')2 receptor; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D011971:Receptors, Immunologic; D005340:Fibrinogen