EFFECT OF A 15-MINUTE INFUSION OF DDAVP ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF (TM)REVASC DURING A 4-HOUR INTRAVENOUS-INFUSION IN HEALTHY MALE-VOLUNTEERS

Plasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of (TM)REVASC before, duri ng and after a DDAVP infusion were investigated. Twelve healthy volunt eers were given an intravenous bolus dose followed by a constant rate four-hour infusion of (TM)REVASC. Fifteen-minute infusions of 0.9% sal ine and DDAVP were started two and three hours respectively after the start of the (TM)REVASC infusion. Plasma (TM)REVASC concentrations wer e not affected by either the saline or DDAVP infusion. (TM)REVASC infu sion produced an increase in APTT which plateaued between 0.5 and 3 ho urs. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the (TM)REVASC infusion continued. There were no serio us adverse events or bleeding episodes throughout the study. In conclu sion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of (TM)REVASC and partially reverses the (TM)R EVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by (TM)REVASC.