Summary
This study establishes a population PK model for FVII clotting activity (FVII:C) after
injection of recombinant activated factor VII (rFVIIa) to healthy volunteers. Twenty
eight volunteers, anticoagulated with acenocoumarol, received one or two rFVIIa injections,
with dose ranging from 5 to 320 μg/kg. The FVII:C kinetic was fitted to a 2 compartment
model, with continuous “endogenous perfusion” mimicking endogenous activity. Estimated
clearance was 2.4 l/h (20% inter-individual variability and 9% inter-period variability).
The volume of distribution at steady-state appeared to be significantly dose dependent:
78 ml/kg for doses ≤20 μg/kg and 88 ml/kg for doses >20 μg/kg respectively, with 16%
inter-individual variability. The dose producing 50% of the maximum drop of INR was
estimated to be 2.2 μg/kg. The model will be used to better define the dosage regimen
for future clinical developments.
