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

PURPOSE: To 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 (14)C-bromfenac ophthalmic solution 0.07%, pH 7.8 with that of (14)C-bromfenac ophthalmic solution 0.09%, pH 8.3, and 2) a 24-hour study evaluating the ocular distribution of (14)C-bromfenac ophthalmic solution 0.07%, pH 7.8. METHODS: In the 12-hour study, rabbits were randomized to receive 50 μL of (14)C-bromfenac 0.07%, pH 7.8 or 50 μL (14)C-bromfenac 0.09%, pH 8.3 in one eye, whereas, in the 24-hour, study both eyes received 50 μL of (14)C-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. RESULTS: Measureable 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 (14)C-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 (14)C-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 (14)C-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 (14)C-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 (14)C-bromfenac levels in the other ocular tissues was the same as that observed in the 12-hour study, with measureable amounts of (14)C-bromfenac detected through 24 hours in all tissues with the exception of vitreous humor. CONCLUSION: Bromfenac 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.