NDLI: Ocular Pharmacokinetic Modeling Using Corneal Absorption and Desorption Rates from in Vitro Permeation Experiments with Cultured Corneal Epithelial Cells

Content Provider	Springer Nature Link
Author	Ranta, Veli Pekka Laavola, Mirka Toropainen, Elisa Vellonen, Kati Sisko Talvitie, Anu Urtti, Arto
Copyright Year	2003
Abstract	Purpose. To determine corneal absorption and desorption rate constants in a corneal epithelial cell culture model and to apply them to predict ocular pharmacokinetics after topical ocular drug application. Method. In vitro permeation experiments were performed with a mixture of six β-blockers using an immortalized human corneal epithelial cell culture model. Disappearance of the compounds from the apical donor solution and their appearance in the basolateral receiver solution were determined and used to calculate the corneal absorption and desorption rate constants. An ocular pharmacokinetic simulation model was constructed for timolol with the Stella$^{®}$ program using the absorption and desorption rate constants and previously published in vivo pharmacokinetic parameters. Results. The corneal absorption rates of β-blockers increased significantly with the lipophilicity of the compounds. The pharmacokinetic simulation model gave a realistic mean residence time for timolol in the cornea (57 min) and the aqueous humor (90 min). The simulated timolol concentration in the aqueous humor was about 1.8 times higher than the previously published experimental values. Conclusions. The simulation model gave a reasonable estimate of the aqueous humor concentration profile of timolol. This was the first attempt to combine cell culture methods and pharmacokinetic modeling for prediction of ocular pharmacokinetics. The wider applicability of this approach remains to be seen.
Starting Page	1409
Ending Page	1416
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	20
Issue Number	9
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2003-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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