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Updated: Jun 6, 2026

Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice
Published on: September 30, 2021
Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following intravenous administration in
H Agersø1, D F Brophy, H Pelzer
1Pharmacology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Maaloev, Denmark. hkag@novonordisk.com
Objective:
The objective of the present study was to evaluate the pharmacokinetics and the clearance pathways of rFVIIa after intravenous administration to hemophilia patients.
Methods:
Ten severe hemophilia patients were included in the study; all patients were intravenously administered a clinically relevant dose of 90 microg kg(-1) (1.8 nmol kg(-1)) rFVIIa. Blood samples were collected consecutively to describe the pharmacokinetics of rFVIIa. All samples were analyzed using three different assays: a clot assay to measure the activity (FVIIa:C), an enzyme immunoassay (EIA) to measure the antigen levels (FVII:Ag), and an EIA (FVIIa-AT) to measure the FVIIa antithrombin III (AT) complex. Pharmacokinetic parameters were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods. A population pharmacokinetic model was used to simultaneously model all three datasets. The total body clearance of rFVIIa:C was estimated to be 38 mL h(-1) kg(-1). The rFVII-AT complex formation was responsible for 65% of the total rFVIIa:C clearance. The initial and the terminal half-life of rFVIIa:C was estimated to be 0.6 and 2.6 h, respectively. The formation of rFVII-AT complex was able to explain the difference observed between the rFVIIa:C and the rFVII:Ag concentration. The non-compartmental analysis resulted in almost identical parameters.
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