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.

Evaluation of aqueous humor concentrations of Istalol and Betimol following a single ocular instillation in rabbit eyes.

PURPOSE: The aim of this study was to evaluate the pharmacokinetic absorption profiles of two commercially available ophthalmic solutions following a single instillation into each eye of New Zealand white rabbit eyes. METHODS: A single dose of either timolol maleate with potassium sorbate (TLA) or timolol hemihydrate (THH) was instilled into each eye of New Zealand white rabbits (15 rabbits/drug preparation, 50-microL dose). Animals were euthanized 15, 30, 60, 120, and 180 min after instillation, with 3 animals/drug/time intervals. Aqueous humor from both eyes of each animal was pooled and analyzed for timolol concentration, using the high-performance liquid chromatography method. RESULTS: TLA reached a mean peak concentration of 3.705 +/- 0.3012 microg/mL at 15 min, tapering to 0.539 +/- 0.1431 microg/mL by 180 min. THH reached a mean peak concentration of 2.239 +/- 0.1430 microg/mL at 15 min postinstillation, tapering to 0.148 +/- 0.0282 microg/mL by 180 min. CONCLUSIONS: TLA containing potassium sorbate demonstrated an absorption profile of more rapid absorption (1.7 fold greater at 15 minutes) and longer residences time (3.6 fold greater at 180 minutes) than the THH. At every time point throughout the study, TLA demonstrated greater drug concentration than THH.

24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits.

PURPOSE: The aim of this study was to determine the distribution and concentrations of bromfenac ophthalmic solution in ocular tissues following topical instillation in New Zealand White (NZW) rabbits. DESIGN: Two animal studies were conducted. METHODS: A single 50-muL (14)C-bromfenac ophthalmic solution (20-25 muCi or 0.09%) was administered into the right eyes of 14-18 randomly assigned NZW rabbits. At various time points, ocular tissues were collected and analyzed for (14)C-bromfenac contents. Ocular tissues were combusted and the amount of radioactivity was determined by liquid scintillation counting (LSC). Aqueous-humor samples were directly transferred to LSC vials. RESULTS: Peak concentrations of (14)C-bromfenac were observed in the aqueous humor and most ocular tissues at or before 2-hours. The highest concentrations were in the cornea, conjunctiva, and sclera. Similar amounts were detected in the aqueous humor, iris-ciliary body, choroid, and, to a slightly lesser degree, in the retina. Measurable amounts of bromfenac were detected in all samples at the 24-hours time point (> or =0.001 mug equivalent/g). CONCLUSIONS: Significant penetration and measurable amounts of (14)C-bromfenac were detected in all ocular tissues over 24 h, including the sclera, choroid, and retina. These results strongly suggest the utility of bromfenac ophthalmic solution 0.09% in treating inflammation of both the anterior and posterior ocular segments.