Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following IV administration in haemophilia patients.

TY - JOUR

T1 - Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following IV administration in haemophilia patients.

AU - Agersø, H

AU - Brophy, D F

AU - Pelzer, H

AU - Martin, E J

AU - Carr, M

AU - Hedner, Ulla

AU - Ezban, M

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200)

PY - 2011

Y1 - 2011

N2 - Objective: The objective of the present study was to evaluate the pharmacokinetics and the clearance pathways of rFVIIa after intravenous administration to haemophilia patients. Methods: Ten severe haemophilia patients were included in the study; all patients were intravenously administered a clinical relevant dose of 90 μg/kg (1.8 nmol/kg) rFVIIa. Blood samples were collected consecutively to describe the pharmacokinetics of rFVIIa. All samples were analysed 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 a 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/kg. 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 hours, respectively. The formation of rFVII-AT complex were able to explain the difference observed between the rFVIIa:C and the rFVII:Ag concentration. The non-compartmental analysis resulted in almost identical parameters.

AB - Objective: The objective of the present study was to evaluate the pharmacokinetics and the clearance pathways of rFVIIa after intravenous administration to haemophilia patients. Methods: Ten severe haemophilia patients were included in the study; all patients were intravenously administered a clinical relevant dose of 90 μg/kg (1.8 nmol/kg) rFVIIa. Blood samples were collected consecutively to describe the pharmacokinetics of rFVIIa. All samples were analysed 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 a 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/kg. 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 hours, respectively. The formation of rFVII-AT complex were able to explain the difference observed between the rFVIIa:C and the rFVII:Ag concentration. The non-compartmental analysis resulted in almost identical parameters.

KW - clearance

KW - pharmacokinetics

KW - NONMEM

KW - modeling

KW - hemophilia patients

KW - rFVIIa

U2 - 10.1111/j.1538-7836.2010.04152.x

DO - 10.1111/j.1538-7836.2010.04152.x

M3 - Article

C2 - 21114621

VL - 9

SP - 333

EP - 338

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 2

ER -