OPEN STUDY OF INTRAVENOUS RECOMBINANT HIRUDIN (CGP-39393) ON PLATELET-FUNCTION AND COAGULATION IN HEALTHY-VOLUNTEERS

Ten healthy male volunteers not previously exposed to hirudin participated in an open trial to evaluate the effects on platelet function and coagulation of recombinant hirudin (rec-hirudin) CGP 39393 1 mg/kg administered intravenously as a bolus injection. The activated partial thromboplastin time (APTT) at 90 minutes, 8 hours and 12 hours after administration, was prolonged by 2.3, 1.4 and 1. 3 times the baseline value, respectively. The APTT was closely correlated with the plasma concentration of rec-hirudin CGP 39393, and was doubled at plasma concentrations of about 60 nmol/L (400, ng/ml). Ex vivo platelet aggregation stimulated by a variety of inducers (except thrombin) was not inhibited. Serum thromboxane B2 and beta-thromboglobulin levels decreased 20 minutes after injection, the reduction being significant only for serum thromboxane B2.