Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling.
CYP
Göttingen Minipig
mass spectrometry
ontogeny
pediatrics
protein abundance
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
02
2021
accepted:
26
02
2021
entrez:
3
5
2021
pubmed:
4
5
2021
medline:
4
5
2021
Statut:
epublish
Résumé
The Göttingen Minipig is gaining ground as nonrodent species in safety testing of drugs for pediatric indications. Due to developmental changes in pharmacokinetics and pharmacodynamics, physiologically based pharmacokinetic (PBPK) models are built to better predict drug exposure in children and to aid species selection for nonclinical safety studies. These PBPK models require high quality physiological and ADME data such as protein abundance of drug metabolizing enzymes. These data are available for man and rat, but scarce for the Göttingen Minipig. The aim of this study was to assess hepatic cytochrome P450 (CYP) protein abundance in the developing Göttingen Minipig by using mass spectrometry. In addition, sex-related differences in CYP protein abundance and correlation of CYP enzyme activity with CYP protein abundance were assessed. The following age groups were included: gestational day (GD) 84-86 (
Identifiants
pubmed: 33935788
doi: 10.3389/fphar.2021.665644
pii: 665644
pmc: PMC8082684
doi:
Types de publication
Journal Article
Langues
eng
Pagination
665644Informations de copyright
Copyright © 2021 Buyssens, De Clerck, Schelstraete, Dhaenens, Deforce, Ayuso, Van Ginneken and Van Cruchten.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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