Ocular metabolism and distribution of drugs in the rabbit eye : Quantitative assessment after intracameral and intravitreal administrations

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del Amo , E M , Hammid , A , Tausch , M , Toropainen , E , Sadeghi , A , Valtari , A , Puranen , J , Reinisalo , M , Ruponen , M , Urtti , A , Sauer , A & Honkakoski , P 2022 , ' Ocular metabolism and distribution of drugs in the rabbit eye : Quantitative assessment after intracameral and intravitreal administrations ' , International Journal of Pharmaceutics , vol. 613 , 121361 . https://doi.org/10.1016/j.ijpharm.2021.121361

Title: Ocular metabolism and distribution of drugs in the rabbit eye : Quantitative assessment after intracameral and intravitreal administrations
Author: del Amo, Eva M.; Hammid, Anam; Tausch, Melanie; Toropainen, Elisa; Sadeghi, Amir; Valtari, Annika; Puranen, Jooseppi; Reinisalo, Mika; Ruponen, Marika; Urtti, Arto; Sauer, Achim; Honkakoski, Paavo
Contributor organization: Division of Pharmaceutical Biosciences
Drug Research Program
Drug Delivery Unit
Drug Delivery
Date: 2022-02-05
Language: eng
Number of pages: 13
Belongs to series: International Journal of Pharmaceutics
ISSN: 0378-5173
DOI: https://doi.org/10.1016/j.ijpharm.2021.121361
URI: http://hdl.handle.net/10138/340262
Abstract: Quantitation of ocular drug metabolism is important, but only sparse data is currently available. Herein, the pharmacokinetics of four drugs, substrates of metabolizing enzymes, was investigated in albino rabbit eyes after intracameral and intravitreal administrations. Acetaminophen, brimonidine, cefuroxime axetil, and sunitinib and their corresponding metabolites were quantitated in the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina with LC-MS/MS analytics. Non-compartmental analysis was employed to estimate the pharmacokinetic parameters of the parent drugs and metabolites. The area under the curve (AUC) values of metabolites were 12-70 times lower than the AUC values of the parent drugs in the tissues with the highest enzymatic activity. The ester prodrug cefuroxime axetil was an exception because it was efficiently and quantitatively converted to cefuroxime in the ocular tissues. In contrast to the liver, sulfotransferases, aldehyde oxidase, and cytochrome P450 3A activities were low in the eye and they had negligible impact on ocular drug clearance. With the exception of esterase substrates, metabolism seems to be a minor player in ocular pharmacokinetics. However, metabolites might contribute to ocular toxicity, and drug metabolism in various eye tissues should be investigated and understood thoroughly.
Subject: Ocular tissues
Acetaminophen
Brimonidine
Cefuroxime
Sunitinib
Sulfotransferase
Aldehyde oxidase
Esterase
CYP3A
Rabbit
Metabolism
Ocular pharmacokinetics
MESSENGER-RNA EXPRESSION
ESTERASE-ACTIVITY
PHARMACOKINETICS
BRIMONIDINE
MONKEY
RAT
BIOACTIVATION
DISPOSITION
INHIBITION
ABSORPTION
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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