Interspecies prediction of pharmacokinetics and tissue distribution of doxorubicin by physiologically-based pharmacokinetic modeling.
allometric scaling
doxorubicin disposition
model validation
pharmacokinetic modeling and simulation
pharmacokinetic-pharmacodynamic
Journal
Biopharmaceutics & drug disposition
ISSN: 1099-081X
Titre abrégé: Biopharm Drug Dispos
Pays: England
ID NLM: 7911226
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
15
10
2019
revised:
18
04
2020
accepted:
22
04
2020
pubmed:
29
4
2020
medline:
19
3
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK) model to describe and predict whole-body disposition of doxorubicin following intravenous administration. The PBPK model was established using previously published data in mice and included 10 tissue compartments: lungs, heart, brain, muscle, kidneys, pancreas, intestine, liver, spleen, adipose tissue, and plasma. Individual tissues were described by either perfusion-limited or permeability-limited models. All parameters were simultaneously estimated and the final model was able to describe murine data with good precision. The model was used for predicting doxorubicin disposition in rats, rabbits, dogs, and humans using interspecies scaling approaches and was qualified using plasma and tissue observed data. Reasonable prediction of the plasma pharmacokinetics and tissue distribution was achieved across all species. In conclusion, the PBPK model developed based on a rich dataset obtained from mice, was able to reasonably predict the disposition of doxorubicin in other preclinical species and humans. Applicability of the model for special populations, such as patients with hepatic impairment, was also demonstrated. The proposed model will be a valuable tool for optimization of exposure profiles of doxorubicin in human patients.
Substances chimiques
Antibiotics, Antineoplastic
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
192-205Subventions
Organisme : Celgene Corporation
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
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