Unravelling the Hepatic Elimination Mechanisms of Colistin.
IVIVE
MRP/Mrp
colistin
hepatic disposition
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
17
10
2022
accepted:
13
05
2023
medline:
14
8
2023
pubmed:
1
6
2023
entrez:
31
5
2023
Statut:
ppublish
Résumé
Colistin is an antibiotic which is increasingly used as a last-resort therapy in critically-ill patients with multidrug resistant Gram-negative infections. The purpose of this study was to evaluate the mechanisms underlying colistin's pharmacokinetic (PK) behavior and to characterize its hepatic metabolism. In vitro incubations were performed using colistin sulfate with rat liver microsomes (RLM) and with rat and human hepatocytes (RH and HH) in suspension. The uptake of colistin in RH/HH and thefraction of unbound colistin in HH (f Slow metabolism was detected in RH/HH, with intrinsic clearance (CL These findings indicate the major role of hepatic metabolism in the non-renal clearance of colistin, while MRP/Mrp-mediated efflux is involved in the hepatic disposition of colistin. Our data provide detailed quantitative insights into the hereto unknown mechanisms responsible for non-renal elimination of colistin.
Identifiants
pubmed: 37258948
doi: 10.1007/s11095-023-03536-7
pii: 10.1007/s11095-023-03536-7
doi:
Substances chimiques
Colistin
Z67X93HJG1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1723-1734Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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