Development of a Plasminogen Population PK model supporting prophylactic replacement therapy for Plasminogen deficient patients within the WAPPS-Hemo platform.

hypoplasminogenemia pharmacokinetics plasminogen deficiency

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:
02 May 2024
Historique:
revised: 10 04 2024
received: 26 01 2024
accepted: 12 04 2024
medline: 3 5 2024
pubmed: 3 5 2024
entrez: 3 5 2024
Statut: aheadofprint

Résumé

Plasminogen deficiency is an ultra rare disease whose patients may develop ligneous lesions if untreated. Prophylactic replacement therapy with plasma derived plasminogen, Ryplazim, is efficient in treating lesions and could benefit from pharmacokinetic (PK) tailoring. The objectives of this study are to develop, evaluate and integrate into the WAPPS-Hemo platform a Population PK model supporting prophylactic replacement therapy for Plasminogen deficient patients. Population PK modelling and evaluations followed the same protocol performed for factor VIII and IX concentrates. Limited sampling analysis used dosing and sampling scenarios in accordance with recommended treatment for Ryplazim. The population PK model, derived from 16 participants included in previous clinical studies, was a 2-compartment model whose variability was best described by fat-free mass. Evaluations showed that the model described well the data and Bayesian forecasting in limited sampling environment led to acceptable precision for PK parameters relevant to plasminogen treatment. The model was integrated into the WAPPS-Hemo webservice to help individualize prophylactic treatment in plasminogen deficient patients. Prospective PK data to be collected through the WAPPS-Hemo database will be used to better understand plasminogen PK and improve patient care.

Identifiants

pubmed: 38698539
doi: 10.1111/hae.15027
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.

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Auteurs

Pierre Chelle (P)

School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.

Dagmar Hajducek (D)

School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.

Karen Thibaudeau (K)

Kedrion, Laval, Quebec, Canada.

Nicholas Hobson (N)

Dept of Health Research Methods, Evidence and Impact and Dept of Medicine, McMaster University, Hamilton, Ontario, Canada.

Alfonso Iorio (A)

Dept of Health Research Methods, Evidence and Impact and Dept of Medicine, McMaster University, Hamilton, Ontario, Canada.

Amy Shapiro (A)

Indiana Hemophilia and Thrombosis Center, Inc., Indianapolis, Indiana, USA.

Andrea Edginton (A)

School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.

Classifications MeSH