Multiple Dosing Increases the Ocular Bioavailability of Topically Administered Flurbiprofen

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Abstract
• The ocular bioavailability of radiolabeled flurbiprofen was determined after single or multiple topical dosing of rabbits. Three doses at half-hour intervals of a 0.03% solution produced higher concentrations in the tissues than those after a single dose of either the 0.03% or the 0.1% solution. Three doses of 0.03% flurbiprofen gave intraocular concentrations in the range that inhibits cyclo-oxygenase activity. Administration of more than three doses did not significantly increase the concentration of flurbiprofen in most tissues. The drug distribution pattern in the ocular tissues after multiple dosing was the same as after single dosing. Although multiple dosing with the 0.03% concentration resulted in higher tissue levels of flurbiprofen, increasing the concentration to 0.1% did not result in greater ocular bioavailability of the drug.