Pharmacokinetic Comparisons of Bromfenac in DuraSite and Xibrom

Purpose: The purpose of this study was to compare the ocular pharmacokinetics of experimental solutions of bromfenac in DuraSite(R) to Xibrom (TM) (bromfenac ophthalmic solution) 0.09%. Methods: The bromfenac content was measured in the aqueous humor of 84 Dutch Belted rabbits after a single dose of either 0.045% or 0.09% bromfenac in DuraSite in the left eye and the commercial preparation in the right eye. The drug content in the aqueous humor was measured at 0.5, 1, 2, 4, 8, 12, and 24 h after instillation. In a separate multi-dose study, rabbits received one drop of the 0.09% experimental or commercial preparation, 3 times daily for 14 days. For both experiments the drug content in ocular tissues was analyzed using liquid chromatography atmospheric pressure ionization tandem mass spectrometry. Results: In single-dose experiments, the concentration of bromfenac in the aqueous humor was higher with the experimental preparations than with the commercial solution. The area under the concentration-time curve of 0.045% and 0.09% bromfenac in DuraSite was similar to 2 and 4-fold higher than that of commercial bromfenac ophthalmic solution, 0.09%. After multi-dose experiments, ocular tissue concentrations of bromfenac were similar to 3 times higher for the experimental than for the commercial formulation. Conclusions: The study demonstrates that the DuraSite topical drug delivery system can deliver bromfenac to various ocular tissues and attain considerably higher concentrations than the commercially available eye drop formulation. The higher aqueous concentration sustained with these experimental formulations could broaden the utility of bromfenac and/or reduce the currently approved dosing frequency of this drug.