In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells.
Blood–brain-barrier
Central nervous system
Nirmatrelvir/ritonavir
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 May 2024
10 May 2024
Historique:
received:
01
11
2023
accepted:
29
04
2024
medline:
11
5
2024
pubmed:
11
5
2024
entrez:
10
5
2024
Statut:
epublish
Résumé
Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC
Identifiants
pubmed: 38729980
doi: 10.1038/s41598-024-60935-5
pii: 10.1038/s41598-024-60935-5
doi:
Substances chimiques
Ritonavir
O3J8G9O825
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10709Informations de copyright
© 2024. The Author(s).
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