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- W3214563990 abstract "We report the pharmacokinetics, biodistribution and metabolism of phospho-sulindac (PS) in a hydrogel formulation efficacious in dry eye disease (DED) administered once daily. PS 0.2% and 0.7% was studied in Dutch-Belted black and New Zealand white rabbits with and without DED. Levels of PS and its metabolites were determined by HPLC. The two rabbit strains gave similar results. PS and its metabolites were limited to the anterior chamber of the eye and undetectable in peripheral blood. DED did not affect the PK, biodistribution or metabolism of PS. Drug levels were dose dependent. PS had a rapid uptake (Tmax 15–30 min) and short t1/2 (0.6–0.9 h), being undetectable at 8h. Of the anterior chamber tissues, cornea and conjunctiva had >90% of the total PS. PS metabolism was rapid and complete, generating all its known in vivo metabolites, except for glucuronidation products. Rabbits with DED had 1.8-fold longer precorneal residence time of PS. The prolonged efficacy of PS despite its limited presence in ocular tissues suggests a vigorous downstream action suppressing ocular surface inflammation of DED. The properties of this formulation, especially the combination of superior efficacy with once-a-day dosing are a major improvement over previous formulations for the treatment of DED." @default.
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- W3214563990 date "2022-01-01" @default.
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- W3214563990 title "Hydrogel formulation of phosphosulindac allows once-a-day ocular dosing and limits its biodistribution to the anterior chamber: Application to dry eye disease treatment" @default.
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- W3214563990 doi "https://doi.org/10.1016/j.jddst.2021.102961" @default.
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