Computational Model of In Vivo Corneal Pharmacokinetics and Pharmacodynamics of Topically Administered Ophthalmic Drug Products.
PBPK
computational modeling
ocular
pharmacodynamics
timolol
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
29
09
2022
accepted:
09
02
2023
medline:
26
4
2023
pubmed:
25
3
2023
entrez:
24
3
2023
Statut:
ppublish
Résumé
Although the eye is directly accessible on the surface of the human body, drug delivery can be extremely challenging due to the presence of multiple protective barriers in eye tissues. Researchers have developed complex formulation strategies to overcome these barriers to ophthalmic drug delivery. Current development strategies rely heavily on in vitro experiments and animal testing to predict human pharmacokinetics (PK) and pharmacodynamics (PD). The primary objective of the study was to develop a high-fidelity PK/PD model of the anterior eye for topical application of ophthalmic drug products. Here, we present a physiologically-based in silico approach to predicting PK and PD in rabbits after topical administration of ophthalmic products. A first-principles based approach was used to describe timolol dissolution, transport, and distribution, including consideration of ionized transport, following topical instillation of a timolol suspension. Using literature transport and response parameters, the computational model described well the concentration-time and response-time profiles in rabbit. Comparison of validated rabbit model results and extrapolated human model results demonstrate observable differences in the distribution of timolol at multiple time points. This modeling framework provides a tool for model-based prediction of PK in eye tissues and PD after topical ophthalmic drug administration to the eyes.
Identifiants
pubmed: 36959411
doi: 10.1007/s11095-023-03480-6
pii: 10.1007/s11095-023-03480-6
doi:
Substances chimiques
Timolol
817W3C6175
Ophthalmic Solutions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
961-975Subventions
Organisme : FDA HHS
ID : U01 FD006929
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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