The ocular distribution of (14)C-labeled bromfenac ophthalmic solution 0.07% in a rabbit model.

Abstract

PurposeTo evaluate the ocular distribution of an advanced formulation of bromfenac ophthalmic solution. Two studies were conducted in rabbits: 1) a 12-hour parallel-group study comparing the ocular distribution of 14C-bromfenac ophthalmic solution 0.07%, pH 7.8 with that of 14C-bromfenac ophthalmic solution 0.09%, pH 8.3, and 2) a 24-hour study evaluating the ocular distribution of 14C-bromfenac ophthalmic solution 0.07%, pH 7.8.MethodsIn the 12-hour study, rabbits were randomized to receive 50 μL of 14C-bromfenac 0.07%, pH 7.8 or 50 μL 14C-bromfenac 0.09%, pH 8.3 in one eye, whereas, in the 24-hour, study both eyes received 50 μL of 14C-bromfenac 0.07%, pH 7.8. Ocular tissues were collected at 1, 2, 4, 8, 12 (both studies) and 24 hours (second study only) following drug instillation, and tissue radioactivity was determined using liquid scintillation chromatography.ResultsMeasureable levels of bromfenac were observed in all ocular tissues, with the exception of vitreous humor, regardless of formulation. In the 12-hour study, high concentrations of 14C-bromfenac were found in the sclera, followed by the iris/ciliary body, aqueous humor, choroid, retina, and lens. There was no significant difference between the bromfenac 0.07%, pH 7.8 and bromfenac 0.09%, pH 8.3 formulations in any 14C-bromfenac tissue levels at any time point, with the exception of in sclera at 2 hours post-instillation (0.451 μg eq/g versus 0.302 μg eq/g, respectively, P<0.001). There was also no significant difference in the total amount of 14C-bromfenac in the tissues evaluated following instillation of the two formulations. In the 24-hour study evaluating bromfenac 0.07%, pH 7.8 only, high concentrations of 14C-bromfenac were found 1 hour post-instillation in the cornea (2.402 μg eq/g) and conjunctiva (1.049 μg eq/g), two tissues not evaluated in the 12-hour study. The rank order of 14C-bromfenac levels in the other ocular tissues was the same as that observed in the 12-hour study, with measureable amounts of 14C-bromfenac detected through 24 hours in all tissues with the exception of vitreous humor.ConclusionBromfenac ophthalmic solution 0.07%, pH 7.8 readily penetrated ocular tissues with levels similar to those of bromfenac ophthalmic solution 0.09%, pH 8.3.