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Abstract：
Several studies showed that repeated topical administration of brimonidine tartrate ophthalmic solution reached the human vitreous concentration above 2 nM, which is the concentration necessary to activate the α2-adrenergic receptor. The purpose of this study was to elucidate the relationship of the brimonidine concentration in the vitreous body to the free concentration in the retina/choroid which is the target site of brimonidine on neuroprotective effect after topical administration.
Brimonidine concentrations in the eye tissues of pigmented rabbits were determined following single ocular administration of 0.1% brimonidine tartrate ophthalmic solution at pH 7.3. Binding affinity of brimonidine to melanin and melanin content in the retina/choroid of pigmented rabbits was also examined. The concentration of free brimonidine which did not bind to melanin in the retina/choroid was calculated using the binding parameters to melanin.
Topically applied brimonidine rapidly distributed to intraocular tissues. The elimination rate from melanin-containing tissues such as the iris/ciliary body and retina/choroid was slower than the aqueous humor and vitreous body in pigmented rabbits. In both the anterior and posterior retina/choroid, the free brimonidine concentrations were over 100-fold lower than the total concentrations. The concentrations in the vitreous body closely matched to the free concentrations in the posterior retina/choroid. Simulated free concentrations in the posterior retina/choroid were gradually increased when 0.1% solution was instilled twice daily.
The present data indicated that the brimonidine concentration in the vitreous body was comparable to the free concentration in the posterior retina/choroid. This suggests that the vitreous concentration can be a surrogate indicator of the free brimonidine concentration in the posterior retina/choroid. From the present findings, it is expected that multiple instillation of brimonidine tartrate ophthalmic solution may produce the sufficient free concentration for activation of the α2-adrenergic receptor in the retina/choroid in human.
Brimonidine concentrations in the eye tissues of pigmented rabbits were determined following single ocular administration of 0.1% brimonidine tartrate ophthalmic solution at pH 7.3. Binding affinity of brimonidine to melanin and melanin content in the retina/choroid of pigmented rabbits was also examined. The concentration of free brimonidine which did not bind to melanin in the retina/choroid was calculated using the binding parameters to melanin.
Topically applied brimonidine rapidly distributed to intraocular tissues. The elimination rate from melanin-containing tissues such as the iris/ciliary body and retina/choroid was slower than the aqueous humor and vitreous body in pigmented rabbits. In both the anterior and posterior retina/choroid, the free brimonidine concentrations were over 100-fold lower than the total concentrations. The concentrations in the vitreous body closely matched to the free concentrations in the posterior retina/choroid. Simulated free concentrations in the posterior retina/choroid were gradually increased when 0.1% solution was instilled twice daily.
The present data indicated that the brimonidine concentration in the vitreous body was comparable to the free concentration in the posterior retina/choroid. This suggests that the vitreous concentration can be a surrogate indicator of the free brimonidine concentration in the posterior retina/choroid. From the present findings, it is expected that multiple instillation of brimonidine tartrate ophthalmic solution may produce the sufficient free concentration for activation of the α2-adrenergic receptor in the retina/choroid in human.
摘要：
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