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M. Abdulrazik, S. Tamilvanan, S. Benita; Ocular and Regional Tissue Distribution of Topically Applied Ocular Therapeutics Part B: Non-Systemic Delivery of Topical Brimonidine to the Brain . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4271.
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Purpose: To date, the risks of central nervous system (CNS) side effects of topically administered ophthalmic therapeutic agents are thought to be the consequence of systemic absorption of these drugs. This paper envisions the possibility of drug delivery to the CNS following ocular application through non-systemic routes. Methods: After single instillation of 50µl of 3H-radiolabeled Alphagan® solution (0.2%) in the cul-de-sac of the right eye, three male albino rabbits (2-2.5 kg) were sacrificed at each time point (5, 15, 30 and 60 min). Both eyes and the brain were dissected. Both sides specimens of aqueous humor, cornea, iris, lens, vitreous, conjunctiva, sclera, ciliary body, choroid, retina, optic nerve, optic tract, olfactory bulb, as well as corpus callosum were weighted, and blood samples were measured. Samples were stored at -80 0C until combustion in tissue oxidizer and radioactive liquid scintillation counting. Results: Significant 3H-brimonidine levels were found in left and right optic nerves and tracts as well as in corpus callosum, with extremely low corresponding drug levels in blood. Uveal tract tissues brimonidine levels were relatively high in the treated eye, and the highest among contralateral eye tissues. Conclusions: Our data provide the first case of good CNS availability after ocular application of conventional ophthalmic therapeutic agent, through non-systemic routes. Although further studies should be done to clarify the mechanism of topical brimonidine penetration to the brain, several questions should be raised regarding the sites of action of topical brimonidine. Similar neuro-ocular pharmacokinetic studies should be adopted as a routine ocular therapeutics evaluation studies.
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