Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following IV administration in haemophilia patients.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1757003
- author
- Agersø, H ; Brophy, D F ; Pelzer, H ; Martin, E J ; Carr, M ; Hedner, Ulla LU and Ezban, M
- organization
- publishing date
- 2011
- 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
- Wiley-Blackwell
- external identifiers
-
- wos:000286626800013
- pmid:21114621
- scopus:79251554994
- pmid:21114621
- ISSN
- 1538-7933
- DOI
- 10.1111/j.1538-7836.2010.04152.x
- language
- English
- LU publication?
- yes
- additional info
- 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)
- 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
- 2016-04-01 10:32:14
- date last changed
- 2022-05-13 17:51:29
@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}},
keywords = {{clearance; pharmacokinetics; NONMEM; modeling; hemophilia patients; rFVIIa}},
language = {{eng}},
number = {{2}},
pages = {{333--338}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1538-7836.2010.04152.x}},
volume = {{9}},
year = {{2011}},
}