Safety, inhibition of platelet aggregation and pharmacokinetics of F(ab′) 2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody FRaMon in high-risk coronary angioplasty

• Published in: Platelets (Edinburgh) Vol. 13; no. 8; pp. 465 - 477
• Main Authors: Mazurov, A.V., Pevzner, D.V., Antonova, O.A., Byzova, T.V., Khaspekova, S.G., Semenov, A.V., Vlasik, T.N., Samko, A.N., Staroverov, I.I., Ruda, M.Ya
• Format: Journal Article
• Language: English
• Published: Informa UK Ltd 01-01-2002; Taylor & Francis
• ISSN: 0953-7104; 1369-1635
• DOI: 10.1080/0953710021000057839

The purpose of the study was to evaluate safety, effects on platelet aggregation and pharmacokinetics of F(ab') 2 fragments of anti-glycoprotein (GP) IIb-IIIa murine monoclonal antibody FRaMon (F(ab') 2 FRaMon) upon its intravenous administration in patients undergoing high-risk coronary angioplasty. Patients were treated before angioplasty with F(ab') 2 FRaMon at 0.2 mg/kg ( n = 17) and 0.25 mg/kg ( n = 12) bolus or with abciximab at 0.25 mg/kg bolus + 12 h infusion at 0.125 w g/kg per min ( n = 29). F(ab') 2 FRaMon at both doses decreased platelet aggregation induced by 20 w M ADP to <10, <20, <40 and <70% of the predrug level at 1, 12, 24 and 72 h after injection, respectively. No significant differences were observed between F(ab') 2 FRaMon and abciximab antiaggregatory effects. In none of the patients did F(ab') 2 FRaMon cause allergic reactions, major bleedings or deep thrombocytopenia. Antibodies against F(ab') 2 FRaMon were detected in one patient. Free F(ab') 2 FRaMon was cleared from plasma within 12 h, while platelet-bound preparation occupied >95, 70-80 and 40-50% of GP IIb-IIIa at 1 and 12-24 h and 3 days after injection, respectively. Thrombotic complications within the first month after angioplasty in groups treated with F(ab') 2 FRaMon and abciximab were observed in one and two patients, respectively. The data obtained have shown that F(ab') 2 FRaMon at bolus administration to patients undergoing coronary angioplasty caused no serious side effects and at comparative dosage inhibited platelet aggregation with the same efficacy as abciximab at bolus + infusion administration.