In silico comparison of pharmacokinetic properties of three extended half-life factor IX concentrates.
Comparative study
Factor IX
Half-life
Hemophilia B
Pharmacokinetics
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
20
10
2020
accepted:
11
02
2021
pubmed:
25
2
2021
medline:
15
12
2021
entrez:
24
2
2021
Statut:
ppublish
Résumé
Pharmacokinetic (PK) differences between the extended half-life (EHL) factor IX (FIX) concentrates for hemophilia B exist, which may influence hemostatic efficacy of replacement therapy in patients. Therefore, we aimed to evaluate the PK properties of three EHL-FIX concentrates and compare them to a standard half-life (SHL) recombinant FIX (rFIX) concentrate. Activity-time profiles of PEGylated FIX (N9-GP), FIX linked with human albumin (rIX-FP), FIX coupled to human IgG1 Fc-domain (rFIXFc), and SHL rFIX were simulated for 10,000 patients during steady-state dosing of 40 IU/kg once weekly (EHL-FIX) and biweekly (rFIX) using published concentrate specific population PK models. Half-lives were respectively 80, 104, and 82 h for N9-GP, rIX-FP, and rFIXFc versus 22 h for rFIX. Between the EHL concentrates, exposure was different with area under the curve (AUC) values of 78.5, 49.6, and 12.1 IU/h/mL and time above FIX target values of 0.10 IU/mL of 168, 168, and 36 h for N9-GP, rIX-FP, and rFIXFc, respectively. N9-GP produced the highest median in vivo recovery value (1.70 IU/dL per IU/kg) compared with 1.18, 1.00, and 1.05 IU/dL per IU/kg for rIX-FP, rFIXFc, and rFIX, respectively. When comparing EHL products, not only half-life but also exposure must be considered. In addition, variation in extravascular distribution of the FIX concentrates must be taken into account. This study provides insight into the different PK properties of these concentrates and may aid in determination of dosing regimens of EHL-FIX concentrates in real-life.
Identifiants
pubmed: 33624121
doi: 10.1007/s00228-021-03111-2
pii: 10.1007/s00228-021-03111-2
pmc: PMC8275546
doi:
Substances chimiques
Delayed-Action Preparations
0
Polyethylene Glycols
3WJQ0SDW1A
Factor IX
9001-28-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1193-1200Informations de copyright
© 2021. The Author(s).
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