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

Research output: Contribution to journalArticle

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.

Details

Authors
  • H Agersø
  • D F Brophy
  • H Pelzer
  • E J Martin
  • M Carr
  • Ulla Hedner
  • M Ezban
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • clearance, pharmacokinetics, NONMEM, modeling, hemophilia patients, rFVIIa
Original languageEnglish
Pages (from-to)333-338
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number2
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

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)