The Effect of Malaria-Induced Alteration of Metabolism on Piperaquine Disposition in Plasmodium yoelii-Infected mice, as Well as Predicted in Malaria Patients.
Malaria
PBPK modeling
clearance
drug metabolizing enzymes
piperaquine
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
07
12
2023
revised:
08
05
2024
accepted:
11
05
2024
medline:
19
5
2024
pubmed:
19
5
2024
entrez:
18
5
2024
Statut:
aheadofprint
Résumé
Malaria-induced alteration of physiological parameters and pharmacokinetic properties of antimalarial drugs may be clinically relevant. Whether and how malaria alters the disposition of piperaquine (PQ) was investigated in this study. The effect of malaria on drug metabolism-related enzymes and PQ pharmacokinetic profiles was studied in Plasmodium yoelii-infected mice in vitro/in vivo. Whether the malaria effect was clinically relevant for PQ was evaluated using a validated physiologically-based pharmacokinetic (PBPK) model with malaria-specific scalars obtained in mice. The infection led to a higher blood-to-plasma partitioning (R The malaria-induced alteration of drug metabolism was substrate-dependent, and its impact on the disposition of PQ and maybe other long-acting aminoquinoline antimalarials was not expected to be clinically relevant.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria-induced alteration of physiological parameters and pharmacokinetic properties of antimalarial drugs may be clinically relevant. Whether and how malaria alters the disposition of piperaquine (PQ) was investigated in this study.
METHODS
METHODS
The effect of malaria on drug metabolism-related enzymes and PQ pharmacokinetic profiles was studied in Plasmodium yoelii-infected mice in vitro/in vivo. Whether the malaria effect was clinically relevant for PQ was evaluated using a validated physiologically-based pharmacokinetic (PBPK) model with malaria-specific scalars obtained in mice.
RESULTS
RESULTS
The infection led to a higher blood-to-plasma partitioning (R
CONCLUSIONS
CONCLUSIONS
The malaria-induced alteration of drug metabolism was substrate-dependent, and its impact on the disposition of PQ and maybe other long-acting aminoquinoline antimalarials was not expected to be clinically relevant.
Identifiants
pubmed: 38761871
pii: S0924-8579(24)00127-4
doi: 10.1016/j.ijantimicag.2024.107209
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107209Informations de copyright
Copyright © 2024. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest None to declare.