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Pharmacokinetics of extended half-life albumin-fused factor IX and heterogeneous F9 variants in hemophilia B: a retrospective cohort study

Title: Pharmacokinetics of extended half-life albumin-fused factor IX and heterogeneous F9 variants in hemophilia B: a retrospective cohort study
Authors: Barbara Lunghi; Massimo Morfini; Silvia Linari; Dario Balestra; Alessio Branchini; Lisa Pieri; Donata Belvini; Laura Banov; Cristina Santoro; Giancarlo Castaman; Francesco Bernardi
Source: Bleeding, Thrombosis and Vascular Biology, Vol 5, Iss 1 (2026)
Publisher Information: PAGEPress Publications
Publication Year: 2026
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Hemophilia B; F9 variants; extended half-life rFIX; pharmacokinetics; clearance; Diseases of the circulatory (Cardiovascular) system; RC666-701
Description: No information is available about the influence exerted by F9 variants on extended half-life (EHL)-recombinant factor IX (rFIX) pharmacokinetics (PK). Adult patients with severe HB (n=41), infused with EHL albumin-fused-rIX-FP, were investigated for key parameters, obtained by Non-Compartmental Analysis (NCA), and for F9 variants, grouped by non-null (n=27) and null (n=14) lesions. Distribution of PK parameters did not differ between genotype groups. However, clearance in the first tertile, including favorable PK profiles, was slower (p=0.003) in patients with null (mean 0.52 mL/h/kg) than in non-null (mean 0.62 mL/h/kg) variants, and non-null genotypes were more frequent in the third tertile (p=0.046). Missense variant bioinformatics analyses predicted more severe disease features in the third than in the first tertile. These exploratory results suggest i) a moderate role of F9 variant type in inter-individual EHL-rFIX clearance variability and ii) differences in F9 genotype-PK NCA parameter association between EHL- and standard half-life-rFIX products.
Document Type: article in journal/newspaper
Language: English
Relation: https://www.btvb.org/btvb/article/view/413; https://doaj.org/toc/2785-5309; https://doaj.org/article/caf70681e1e24eac8c72b3f028756254
DOI: 10.4081/btvb.2026.413
Availability: https://doi.org/10.4081/btvb.2026.413; https://doaj.org/article/caf70681e1e24eac8c72b3f028756254
Accession Number: edsbas.71BACB58
Database: BASE