Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail : Tissue exposures in the rabbit eye

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Fayyaz , A , Vellonen , K-S , Ranta , V-P , Toropainen , E , Reinisalo , M , Valtari , A , Puranen , J , Ricci , G DA , Heikkinen , E M , Gardner , I , Ruponen , M , Urtti , A , Jamei , M & Amo , E M D 2021 , ' Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail : Tissue exposures in the rabbit eye ' , European Journal of Pharmaceutics and Biopharmaceutics , vol. 166 , pp. 155-162 . https://doi.org/10.1016/j.ejpb.2021.06.003

Title: Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail : Tissue exposures in the rabbit eye
Author: Fayyaz, Anam; Vellonen, Kati-Sisko; Ranta, Veli-Pekka; Toropainen, Elisa; Reinisalo, Mika; Valtari, Annika; Puranen, Jooseppi; Ricci, Giuseppe D'Amico; Heikkinen, Emma M.; Gardner, Iain; Ruponen, Marika; Urtti, Arto; Jamei, Masoud; Amo, Eva M. del
Other contributor: University of Helsinki, Drug Research Program



Date: 2021-09
Language: eng
Number of pages: 8
Belongs to series: European Journal of Pharmaceutics and Biopharmaceutics
ISSN: 0939-6411
DOI: https://doi.org/10.1016/j.ejpb.2021.06.003
URI: http://hdl.handle.net/10138/333103
Abstract: Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.
Subject: Timolol
Betaxolol
Atenolol
Ocular pharmacokinetics
Rabbit
Topical
Intracameral
Corneal route
Conjunctival-scleral route
SYSTEMIC ABSORPTION
BETA-BLOCKERS
PENETRATION ROUTES
DRUG DIFFUSION
CONJUNCTIVAL
PERMEABILITY
PILOCARPINE
CORNEAL
FLUORESCEIN
CLEARANCE
317 Pharmacy
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