Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol

• Published in: Thrombosis and haemostasis Vol. 80; no. 1; p. 109
• Main Authors: Girard, P, Nony, P, Erhardtsen, E, Delair, S, Ffrench, P, Dechavanne, M, Boissel, J P
• Format: Journal Article
• Language: English
• Published: Germany 01-07-1998
• Subjects: Acenocoumarol - therapeutic use; Anticoagulants - therapeutic use; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Factor VIIa - pharmacokinetics; Humans; Logistic Models; Recombinant Proteins - pharmacokinetics; Reference Values
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1615148

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 microg/kg. The FVII:C kinetic was fitted to a 2 compartment model, with continuous "endogenous perfusion" mimicking endogenous activity. Estimated clearance was 2.4 1/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 < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively, with 16% inter-individual variability. The dose producing 50% of the maximum drop of INR was estimated to be 2.2 microg/kg. The model will be used to better define the dosage regimen for future clinical developments.