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 microg/kg per min (n = 29). F(ab')(2)
FRaMon at both doses decreased platelet aggregation induced by 20 microM
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.