Limited sampling strategies for accurate determination of extended half-life factor VIII pharmacokinetics in severe haemophilia A patients.
Bayesian forecasting
extended half-life
factor VIII
haemophilia A
population pharmacokinetics
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
revised:
13
02
2021
received:
08
09
2020
accepted:
15
02
2021
pubmed:
21
3
2021
medline:
25
9
2021
entrez:
20
3
2021
Statut:
ppublish
Résumé
Extended half-life (EHL) factor VIII (FVIII) products may decrease the burden of prophylactic treatment in haemophilia A by reducing infusion frequency. However, these products still exhibit wide inter-patient variability and benefit from pharmacokinetic (PK) tailoring. Identify limited sampling strategies for rFVIIIFc, an EHL FVIII product, that produce accurate estimates of PK parameters and relevant troughs. We performed a limited sampling analysis on simulated populations of adults, adolescents, and children based on published population PK data. Sampling strategies were evaluated by comparing the error in estimates of half-life, clearance, and trough levels, to a full 6-sample design. Furthermore, we assessed the impact of incorporating knowledge about prior doses, and the day of the PK study within the regimen. We also evaluated the potential inappropriate dose adjustment rate (IDAR) among the modelled sampling strategies. Many sampling strategies, including several 2-sample designs, accurately predicted the PK and exposure measures (median absolute error <10%). When samples are only collected during a single visit (i.e., predose + peak), inclusion of prior dose information reduces median half-life error from >20% to ~5% for adults/adolescents. In this same scenario, appropriate scheduling of the PK study decreases likelihood of unmeasurable predose samples, reducing median error on the 72-h trough from 25% to <12% in the youngest population. The PK of rFVIIIFc can be accurately estimated using only peak and trough samples, provided that knowledge of prior doses is incorporated and the PK study is planned on an appropriate day within the dosing regimen.
Sections du résumé
BACKGROUND
BACKGROUND
Extended half-life (EHL) factor VIII (FVIII) products may decrease the burden of prophylactic treatment in haemophilia A by reducing infusion frequency. However, these products still exhibit wide inter-patient variability and benefit from pharmacokinetic (PK) tailoring.
OBJECTIVE
OBJECTIVE
Identify limited sampling strategies for rFVIIIFc, an EHL FVIII product, that produce accurate estimates of PK parameters and relevant troughs.
METHODS
METHODS
We performed a limited sampling analysis on simulated populations of adults, adolescents, and children based on published population PK data. Sampling strategies were evaluated by comparing the error in estimates of half-life, clearance, and trough levels, to a full 6-sample design. Furthermore, we assessed the impact of incorporating knowledge about prior doses, and the day of the PK study within the regimen. We also evaluated the potential inappropriate dose adjustment rate (IDAR) among the modelled sampling strategies.
RESULTS
RESULTS
Many sampling strategies, including several 2-sample designs, accurately predicted the PK and exposure measures (median absolute error <10%). When samples are only collected during a single visit (i.e., predose + peak), inclusion of prior dose information reduces median half-life error from >20% to ~5% for adults/adolescents. In this same scenario, appropriate scheduling of the PK study decreases likelihood of unmeasurable predose samples, reducing median error on the 72-h trough from 25% to <12% in the youngest population.
CONCLUSIONS
CONCLUSIONS
The PK of rFVIIIFc can be accurately estimated using only peak and trough samples, provided that knowledge of prior doses is incorporated and the PK study is planned on an appropriate day within the dosing regimen.
Identifiants
pubmed: 33742733
doi: 10.1111/hae.14288
pmc: PMC9584106
mid: NIHMS1832737
doi:
Substances chimiques
Hemostatics
0
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
408-416Subventions
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : American Lebanese Syrian Associated Charities
Organisme : CIHR
Pays : Canada
Organisme : Center for Strategic Scientific Initiatives, National Cancer Institute
ID : CA21765
Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Haemophilia. 2016 Jul;22(4):e245-50
pubmed: 27216992
Ther Drug Monit. 2007 Feb;29(1):20-6
pubmed: 17304146
Haemophilia. 2010 Jul 1;16(4):597-605
pubmed: 20148977
J Blood Med. 2016 Sep 12;7:187-198
pubmed: 27695377
Vital Health Stat 3 Anal Stud. 2016 Aug;(39):1-46
pubmed: 28437242
Blood. 2012 Mar 29;119(13):3031-7
pubmed: 22223821
Drugs. 2016 Sep;76(13):1281-1291
pubmed: 27487799
J Thromb Haemost. 2015 Jun;13(6):967-77
pubmed: 25912075
Expert Opin Drug Metab Toxicol. 2016 Nov;12(11):1313-1321
pubmed: 27539370
Blood. 2014 Jan 16;123(3):317-25
pubmed: 24227821
Eur J Haematol. 2015 Dec;95 Suppl 81:30-5
pubmed: 26679395
J Thromb Haemost. 2017 Dec;15(12):2461-2465
pubmed: 29119666
Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):163-74
pubmed: 27140796