Translational physiologically-based pharmacokinetic model for ocular disposition of monoclonal antibodies.
Antibody
Eye
Human
Monkey
Ocular Pharmacokinetics
Physiologically-Based pharmacokinetic model
Journal
Journal of pharmacokinetics and pharmacodynamics
ISSN: 1573-8744
Titre abrégé: J Pharmacokinet Pharmacodyn
Pays: United States
ID NLM: 101096520
Informations de publication
Date de publication:
09 Aug 2023
09 Aug 2023
Historique:
received:
26
12
2022
accepted:
27
07
2023
medline:
10
8
2023
pubmed:
10
8
2023
entrez:
9
8
2023
Statut:
aheadofprint
Résumé
We have previously published a PBPK model comprising the ocular compartment to characterize the disposition of monoclonal antibodies (mAbs) in rabbits. While rabbits are commonly used preclinical species in ocular research, non-human primates (NHPs) have the most phylogenetic resemblance to humans including the presence of macula in the eyes as well as higher sequence homology. However, their use in ocular research is limited due to the strict ethical guidelines. Similarly, in humans the ocular samples cannot be collected except for the tapping of aqueous humor (AH). Therefore, we have translated this rabbit model to monkeys and human species using literature-reported datasets. Parameters describing the tissue volumes, physiological flows, and FcRn-binding were obtained from the literature, or estimated by fitting the model to the data. In the monkey model, the values for the rate of lysosomal degradation for antibodies (K
Identifiants
pubmed: 37558929
doi: 10.1007/s10928-023-09881-9
pii: 10.1007/s10928-023-09881-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : GM114179
Pays : United States
Organisme : NCI NIH HHS
ID : CA246785
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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