PBPK modeling of recombinant factor IX Fc fusion protein (rFIXFc) and rFIX to characterize the binding to type 4 collagen in the extravascular space.

ABSTRACT: Patients with severe and sometimes moderate hemophilia B are prophylactically treated with factor IX concentrates to prevent bleeding. For some time now, various extended terminal half-life (EHL) recombinant factor IX concentrates are available allowing less frequent administration during prophylaxis in comparison to standard half-life recombinant FIX (rFIX). Especially, recombinant FIX-Fc fusion protein (rFIXFc; Alprolix®) exhibits a rapid distribution phase, potentially due to binding to type IV collagen (Col4) in the extravascular space. Studies suggest that the presence of extravascular rFIXFc is protective against bleeding as without measurable FIX activity in plasma, and no extra bleeding seems to occur. The physiologically based pharmacokinetic (PBPK) model for rFIXFc which we descr

SUBMITTER: Cloesmeijer ME 

PROVIDER: S-EPMC11494894 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature