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- W4200108623 endingPage "121361" @default.
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- W4200108623 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." @default.
- W4200108623 created "2021-12-31" @default.
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- W4200108623 date "2022-02-01" @default.
- W4200108623 modified "2023-10-16" @default.
- W4200108623 title "Ocular metabolism and distribution of drugs in the rabbit eye: Quantitative assessment after intracameral and intravitreal administrations" @default.
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- W4200108623 doi "https://doi.org/10.1016/j.ijpharm.2021.121361" @default.
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