Ocular Distribution of Brimonidine and Brinzolamide after Topical Instillation of a 0.1% Brimonidine Tartrate and 1% Brinzolamide Fixed-Combination Ophthalmic Suspension: An Interventional Study

Abstract

Purpose: To evaluate the concentrations of brimonidine and brinzolamide in the vitreous and aqueous humor after instillation of a 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. Methods: The present investigation involved patients with macular holes or idiopathic epiretinal membranes who were planning to undergo vitrectomy. One week prior to surgery, the patients received twice-daily topical treatment with 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. Before vitrectomy, vitreous and aqueous humor samples were collected, and the mean concentrations of brimonidine and brinzolamide were determined through liquid chromatography-tandem spectrometry. Results: Ten eyes (nine phakic and one pseudophakic eyes; 10 patients) were examined. The concentration of brimonidine in vitreous and aqueous humor samples was 5.02 ± 2.24 and 559 ± 670 nM, respectively. The concentration of brimonidine in the vitreous humor, which is needed to activate α2 receptors, was >2 nM in all patients. The concentration of brinzolamide was 8.96 ± 4.65 and 1100 ± 813 nM, respectively. However, there was no significant correlation between the concentrations of brimonidine in the vitreous and aqueous humor samples. Conclusions: Sufficient concentrations of brimonidine were detected in all vitreous samples. The dissociated correlation of the drug concentrations between aqueous and vitreous humors implies the possibility of another pathway to vitreous humor, different from the pathway to aqueous humor.

Patient Factors Influencing Intraocular Penetration of Brimonidine-Related Eye Drops in Adults: A Post Hoc Pooled Analysis

“…This post hoc pooled analysis integrated and reanalyzed data sourced from three clinical studies that determined brimonidine concentrations in the aqueous and vitreous humor after the topical application of the following eye drops containing brimonidine: 0.1% brimonidine tartrate ophthalmic solution (Aiphagan Ò ; Senju Pharmaceutical Co., Ltd., Osaka, Japan), 0.1% brimonidine tartrate and 0.5% timolol (equivalent to 0.68% timolol maleate) fixedcombination ophthalmic solution (Aibeta Ò ; Senju Pharmaceutical Co., Ltd.) and 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination suspension (Ailamide Ò ; Senju Pharmaceutical Co., Ltd.) [8][9][10] (Tables 1 and 2).…”

“…No correlation was found among brimonidine, timolol or brinzolamide concentrations in the aqueous and vitreous humor and corneal thickness, corneal endothelial cell density, tear secretion (Schirmer's test), eye axial length, height or BMI (Figs. 5,6,7,8,9,10).…”

The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits

“…While α2 agonists have been reported to cause vasoconstriction in some capillaries [46][47][48], they have been shown to cause vasodilation in other, larger vessels [47,49,50]. In the eye, it has been reported that BBFC eye drops reach the vitreous body and retinal vessels [51]. When the vitreous concentration of brimonidine surpasses the threshold for α2 adrenergic receptor activation [52], the expression of endothelial nitric oxide synthase (eNOS) increases, inducing NO, which has a vasodilating effect on the vasculature, including in the retinal vessels [53].…”