Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?
Fiche publication
Date publication
avril 2020
Journal
Pharmaceutics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NGUYEN Philippe
Tous les auteurs :
Allard Q, Djerada Z, Pouplard C, Repessé Y, Desprez D, Galinat H, Frotscher B, Berger C, Harroche A, Ryman A, Flaujac C, Chamouni P, Guillet B, Volot F, Szymezak J, Nguyen P, Cazaubon Y
Lien Pubmed
Résumé
We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.
Mots clés
dose tailoring, factor VIII, modelling, pharmacokinetics, severe haemophilia A, switch
Référence
Pharmaceutics. 2020 Apr 21;12(4):