Effect of Solution pH on Distribution of Ophthalmically Administered Brimonidine in Posterior Ocular Tissues in Pigmented Rabbits

Abstract

Introduction Brimonidine bioavailability in the aqueous humor depends on the solution pH following topical administration. The purpose of this study was to investigate the effect of solution pH on brimonidine distribution in the posterior ocular tissues in pigmented rabbits. Methods The anterior retina/choroid, posterior retina/choroid, and vitreous body of pigmented rabbits were collected 0.67, 1.5, 3, 6, 12, 24, 168, and 360 h after the administration of a single topical dose of 0.2% brimonidine tartrate ophthalmic solution, pH 6.4 (Alphagan ® ; Allergan Inc., Irvine, CA, USA). Brimonidine concentrations in these tissues were quantified using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were determined using noncompartmental analysis, and the results were compared with tissues from eyes administered 0.1% brimonidine tartrate ophthalmic solution, pH 7.3 (Aiphagan ® ; Senju Pharmaceutical Co., Ltd., Osaka, Japan) in our previous study conducted using the same procedure. Results Topically applied brimonidine was distributed rapidly into the posterior tissues of the eye after a single ophthalmic administration of the 0.2% ophthalmic solution. The areas under the curve from time 0 to 360 h following dosing with the 0.2% ophthalmic solution were 500,000, 14,300, and 28.7 ng h/g in the anterior and posterior retina/choroid, and vitreous body, respectively. Conclusion The differences in the areas under the curve between two ophthalmic solutions were less than the difference in drug concentrations between these two products in any tissues. This finding indicates that the change in the solution pH from 6.4 to 7.3 increases brimonidine bioavailability into the posterior ocular tissues similarly as into the aqueous humor. Funding Senju Pharmaceutical Co., Ltd.

In Vitro and In-Eye Comparison of Commercial Pilocarpine Ophthalmic Solution and an Optimized, Reformulated Pilocarpine for Presbyopia Treatment

“…In addition, the ocular bioavailability of the generic pilo is low (1-3%) [27], given that most of the drug in the tear film is in a protonated or ionized form that poorly crosses the cornea [11]. The immediate rise in pH rapidly increases the nonionized proportion of pilo on the ocular surface, which may improve bioavailability because of higher membrane permeability [28]. This increased bioavailability translates to effective drug delivery to the anterior segment [10] and may contribute to the long duration of action.…”