Effect of a 15-Minute Infusion of DDAVP on the Pharmacokinetics and Pharmacodynamics of ™REVASC during a Four-Hour Intravenous Infusion in Healthy Male Volunteers

Summary

Plasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of ™REVASC before, during and after a DDAVP infusion were investigated.

Twelve healthy volunteers were given an intravenous bolus dose followed by a constant rate four-hour infusion of ™REVASC. Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three hours respectively after the start of the ™REVASC infusion.

Plasma ™REVASC concentrations were not affected by either the saline or DDAVP infusion. ™REVASC infusion produced an increase in APTT which plateaued between 0.5 and 3 hours. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the ™REVASC infusion continued. There were no serious adverse events or bleeding episodes throughout the study.

In conclusion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of ™REVASC and partially reverses the ™REVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by ™REVASC.

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