Premium
Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following intravenous administration in hemophilia patients
Author(s) -
AGERSØ H.,
BROPHY D. F.,
PELZER H.,
MARTIN E. J.,
CARR M.,
HEDNER U.,
EZBAN M.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.04152.x
Subject(s) - pharmacokinetics , recombinant factor viia , clearance , medicine , pharmacology , population , antithrombin , anesthesia , heparin , urology , environmental health
Summary. 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 μg 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.