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

Abstract

SummaryPlasma 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.

Ddavp Is Not a Panacea for Children With Bleeding Disorders

“…DDAVP shortened the prolonged PTT and BT of patients taking heparin ( Schulman & Johnsson, 1991) and of volunteers taking hirudin, which may represent a role for DDAVP in the partial reversal of anticoagulation induced by hirudin ( Amin et al , 1997 ). DDAVP also counteracted the F VIII depletion observed after hydroxyethyl starch (HES) administration and was considered as a treatment option for the mild coagulopathy infrequently associated with HES administration ( Conroy et al , 1996 ).…”

Direkte Thrombininhibitoren

“…Desmopressin konnte die Verlängerung der aPTT unter Lepirudin in vitro und bei Probanden normalisieren [83,84]. Im Tierversuch konnte eine Reduktion des Blutverlustes und der Gerinnungszeiten nach Desmopressin gezeigt werden [85,86].…”

Hirudine zur Behandlung der heparininduzierten Thrombozytopenie und zur Thromboseprophylaxe

“…Ein spezifisches Antidot für Hirudin steht nicht zur Verfügung. DDAVP (Desmopressin) bewirkte bei Gesunden eine dosisabhängige Reduktion der hirudininduzierten aPTT-Verlängerung (1,49). Prothrombinkomplexkonzentrat wurde zur Behandlung von hirudininduzierten Blutungskomplikationen erfolgreich eingesetzt (50).…”