Target-mediated disposition population pharmacokinetics model of erythropoietin in premature neonates following multiple intravenous and subcutaneous dosing regimens.
Erythropoietin
Population pharmacokinetics
Premature neonates
Target-mediated drug disposition
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
01 Oct 2019
01 Oct 2019
Historique:
received:
09
04
2019
revised:
16
06
2019
accepted:
18
07
2019
pubmed:
25
7
2019
medline:
6
2
2020
entrez:
25
7
2019
Statut:
ppublish
Résumé
Routine erythropoietin (Epo) therapy for neonatal anemia is presently controversial due to its modest response. We speculate that an important contributor to this modest response is that previous clinical study designs were not driven by rigorous mechanistic and kinetic insights into the complex pharmacokinetics (PK) and pharmacodynamics (PD) of Epo in this population. To address this therapeutic opportunity, we conducted a prospective clinical study to investigate the PK of Epo in very-low-birth-weight (VLBW) premature neonates using a unique Epo dosing algorithm that accounts for complex neonatal erythropoietic physiology. Twenty-seven subjects received up to 10 intravenous or subcutaneous exogenous doses of Epo (600 or 1200 U/kg) during the first 4 weeks of life. Subjects were administered two doses of Epo 1200 U/kg on days 2 and 16, and eight doses of Epo 600 U/kg on days 4, 5, 6, 7, 9, 14, 15, and 28 following birth. We have developed for the first time a mechanistic, target-mediated disposition model that provides novel insights into the mechanisms driving Epo PK in VLBW neonates. Epo association rate, k
Identifiants
pubmed: 31340188
pii: S0928-0987(19)30276-3
doi: 10.1016/j.ejps.2019.105013
pmc: PMC6733583
mid: NIHMS1537230
pii:
doi:
Substances chimiques
Erythropoietin
11096-26-7
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105013Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL046925
Pays : United States
Organisme : NCATS NIH HHS
ID : U54 TR001356
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002537
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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