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: Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A.
    Author: Tiede A, Brand B, Fischer R, Kavakli K, Lentz SR, Matsushita T, Rea C, Knobe K, Viuff D.
    Journal: J Thromb Haemost; 2013 Apr; 11(4):670-8. PubMed ID: 23398640.
    Abstract:
    BACKGROUND: N8-GP is a recombinant factor VIII (FVIII) with a site-directed glycoPEGylation for the purpose of half-life prolongation. OBJECTIVES: To evaluate the safety and pharmacokinetic profiles of N8-GP in comparison with those of the patients' previous FVIII products. PATIENTS/METHODS: This dose-escalation trial included previously treated patients with severe hemophilia A who received one of three dose levels (25, 50 or 75 U kg(-1) ) of N8-GP and FVIII product. Each dose escalation was preceded by safety and pharmacokinetic assessment. The trial was registered at www.clinicaltrials.gov (NCT01205724). RESULTS: Twenty-six patients each received one dose of their previous FVIII product followed by the same, single dose of N8-GP. N8-GP, at any tested dose, was well tolerated, with a low frequency of adverse events. No new inhibitors against FVIII or N8-GP and no binding antibodies against N8-GP developed during the trial. The pharmacokinetics of N8-GP were dose-linear. The incremental recovery of N8-GP was 0.025 [(U mL(-1) )/(U kg(-1) )]. The clearance was 1.79 mL(-1)  h(-1)  kg(-1) . The estimated time from dosing of 50 U kg(-1) N8-GP to a plasma activity of 1% was 6.5 days (range: 3.6-7.9 days). The mean terminal half-life of N8-GP was 19.0 h (range: 11.6-27.3 h), 1.6-fold longer than that of the patients' previous products. CONCLUSIONS: A single dose of up to 75 U kg(-1) N8-GP was well tolerated in patients with hemophilia A, with no safety concerns. N8-GP had a prolonged half-life, and FVIII:C activity remained at > 1% for longer than the patient's previous product. These results indicate that N8-GP has the potential to reduce dosing frequency during prophylaxis.
    [Abstract] [Full Text] [Related] [New Search]