Pharmacokinetics, efficacy and safety of a novel fibrinogen concentrate in pediatric patients with congenital afibrinogenemia.
Journal
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
ISSN: 1473-5733
Titre abrégé: Blood Coagul Fibrinolysis
Pays: England
ID NLM: 9102551
Informations de publication
Date de publication:
01 Jan 2023
01 Jan 2023
Historique:
pubmed:
10
12
2022
medline:
7
1
2023
entrez:
9
12
2022
Statut:
ppublish
Résumé
Congenital afibrinogenemia treatment with plasma-derived fibrinogen concentrates in pediatric patients is limited. This study investigated the pharmacokinetics, surrogate efficacy, and safety of a plasma-derived fibrinogen concentrate (FIB Grifols) in pediatric patients with congenital afibrinogenemia. Patients aged <18 years old diagnosed with congenital afibrinogenemia were included in this prospective, multinational, phase 1-2, single-arm study. After a single dose of a plasma-derived fibrinogen concentrate (70 mg/kg body weight), pharmacokinetic parameters were determined from plasma fibrinogen activity (Clauss method) and antigen method (ELISA), and calculated by noncompartmental and population pharmacokinetic (popPK) models. Patients were followed up over 14 days. Efficacy variables were the mean change on thromboelastographic variables (maximum clot firmness [MCF], alpha angle [ α ]) and coagulation tests (prothrombin time, activated partial thromboplastin time, and thrombin time) 1 h postinfusion. Safety parameters were assessed. Eleven patients with a median (range) age 8.80 (3.7-12.7) years were treated with the plasma-derived fibrinogen concentrate. Using the popPK modeling, fibrinogen activity reached a mean (standard deviation) Cmax of 1.3 (0.225) g/l, half-life ( t1/2 ) of 60.6 (4.48) h and incremental in vivo recovery (IVR) of 1.86 (0.322) (mg/dl)/(mg/kg). Surrogate efficacy was demonstrated by significant increase in MCF (9.23 [3.94] mm; P < 0.001; 95% confidence interval 6.58, 11.87). All coagulation times were significantly shortened after fibrinogen concentrate infusion. Adverse events were mild or moderate in severity, and unrelated to fibrinogen concentrate. In pediatric patients with congenital afibrinogenemia, plasma-derived fibrinogen concentrate revealed a favorable and specific pharmacokinetic profile, demonstrated efficacy in coagulation and was safe and well tolerated.
Identifiants
pubmed: 36484281
doi: 10.1097/MBC.0000000000001182
pii: 00001721-202301000-00009
doi:
Substances chimiques
Fibrinogen
9001-32-5
Hemostatics
0
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-69Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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