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  • Title: Antiplatelet and antithrombotic effects of orbofiban, a new orally active GPIIb/IIIa antagonist, in guinea pigs.
    Author: Ogawa T, Sugidachi A, Naganuma H, Asai F.
    Journal: Thromb Res; 2000 Mar 01; 97(5):307-15. PubMed ID: 10709906.
    Abstract:
    Antiplatelet and antithrombotic effects of orbofiban, a new orally active glycoprotein IIb/IIIa antagonist, were evaluated in guinea pigs. SC-57101A (0.03-1 microM), the hydrochloride salt of the active form of orbofiban, inhibited in vitro ADP- and collagen-induced platelet aggregation in a concentration-dependent manner. Oral administration of orbofiban (3-30 mg/kg) resulted in dose-dependent inhibition of ADP- and collagen-induced platelet aggregation. The inhibition peaked at 1-2 hours postdose and then declined slowly. The agent also showed similar inhibition of platelet aggregation in guinea pigs with dietary-induced hypercholesterolemia. In contrast, the antiaggregatory effects of acetylsalicylic acid differed more widely between normal and hyperlipidemic animals compared to those of orbofiban. Plasma concentration of the active form, measured by a column-switching HPLC method, correlated well with the inhibition of platelet aggregation. Orbofiban (3-100 mg/kg, p.o.) caused dose-dependent inhibition of thrombus formation in an arteriovenous-shunt-thrombosis model. Orbofiban at high doses (> or =30 mg/kg) and acetylsalicylic acid (100 mg/kg) both prolonged cutaneous bleeding time measured by the template method. These results demonstrate that orbofiban is an orally active and potent inhibitor of platelet aggregation with an efficacy that correlates well with the plasma concentration of its active form.
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