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

Agersø, H; Brophy, D F; Pelzer, H; Martin, E J; Carr, M; Hedner, Ulla LU and Ezban, M (2011) In Journal of Thrombosis and Haemostasis 9(2). p.333-338
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
clearance, pharmacokinetics, NONMEM, modeling, hemophilia patients, rFVIIa
in
Journal of Thrombosis and Haemostasis
volume
9
issue
2
pages
333 - 338
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000286626800013
  • pmid:21114621
  • scopus:79251554994
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2010.04152.x
language
English
LU publication?
yes
id
2e6ab8ff-4ee3-4591-acda-50660413a67a (old id 1757003)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21114621?dopt=Abstract
date added to LUP
2011-01-03 11:21:41
date last changed
2017-05-21 03:14:25
@article{2e6ab8ff-4ee3-4591-acda-50660413a67a,
  abstract     = {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.},
  author       = {Agersø, H and Brophy, D F and Pelzer, H and Martin, E J and Carr, M and Hedner, Ulla and Ezban, M},
  issn         = {1538-7933},
  keyword      = {clearance,pharmacokinetics,NONMEM,modeling,hemophilia patients,rFVIIa},
  language     = {eng},
  number       = {2},
  pages        = {333--338},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following IV administration in haemophilia patients.},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2010.04152.x},
  volume       = {9},
  year         = {2011},
}