These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacokinetics and pharmacodynamics of a new recombinant FVIII (N8) in haemophilia A mice.
    Author: Elm T, Karpf DM, Øvlisen K, Pelzer H, Ezban M, Kjalke M, Tranholm M.
    Journal: Haemophilia; 2012 Jan; 18(1):139-45. PubMed ID: 21771205.
    Abstract:
    N8 is a new recombinant factor VIII (rFVIII) compound produced and formulated without human- or animal-derived protein. The aims of the present studies were to evaluate the pharmacokinetics and pharmacodynamics properties of N8 and to compare with a commercially available rFVIII product (Advate(®)) in haemophilia A mice. The pharmacokinetics were evaluated after single i.v. administration of 80, 120 and 280 IU kg(-1) of N8 and Advate(®) and measurements of FVIII blood concentrations as a function of time. The efficacy and dose response curves of N8 and Advate(®) (1-200 IU kg(-1)) were evaluated in a tail bleeding model. Furthermore, the effects in a newly developed haemophilia knee joint haemarthrosis model were investigated. No significant differences were found in the pharmacokinetic parameters between N8 and Advate(®). The clearances were 11 ± 1 vs. 10 ± 2 mL h(-1) kg(-1) (P = 0.14) and the half-lives 7.2 ± 0.9 vs. 7.7 ± 1.4 h (P = 0.31) after administration of N8 and Advate(®) respectively. Dose-independent pharmacokinetics was shown, and comparable efficacy and potency were shown between N8 and Advate(®) in the tail bleeding model. Both compounds normalized the bleeding at the dose of 200 IU kg(-1), and for blood loss ED(50) values of 27 IU kg(-1) (N8) and 28 IU/kg (Advate(®)) were found (P = 0.97). In the haemarthrosis model, treatment with N8 and Advate(®) at 200 IU kg(-1) reduced the mean increase in the joint diameter significantly from 1.23 ± 0.19 to 0.32 ± 0.08 mm (P < 0.01) and 0.25 ± 0.08 mm (P < 0.001) respectively. Pharmacokinetics and pharmacodynamics of N8 and Advate(®) were comparable after i.v. administration to haemophilia A mice.
    [Abstract] [Full Text] [Related] [New Search]