TY - JOUR
T1 - Non-systemic delivery of topical brimonidine to the brain
T2 - A neuro-ocular tissue distribution study
AU - Tamilvanan, Shunmugaperumal
AU - Abdulrazik, Muhammad
AU - Benita, Simon
PY - 2006/12
Y1 - 2006/12
N2 - 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. After single instillation of 50 μl 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 sides (eyes) specimens of aqueous humor, cornea, iris, lens, vitreous, conjunctiva, sclera, ciliary body, choroid, retina, optic nerve, optic tract and olfactory bulb were weighed, and blood samples were measured, before combustion in tissue oxidizer and radioactive liquid scintillation counting. Significant 3H-brimonidine levels were found in right and left optic nerves and tracts with extremely low corresponding drug levels in blood. Uveal tract (ciliary body, iris and choroid tissues) brimonidine levels were relatively high in the treated eye, and the highest among contralateral eye tissues. Our data provide the first case of good CNS availability after ocular application of conventional ophthalmic therapeutic agent, through non-systemic routes. Similar neuro-ocular pharmacokinetic studies should be adopted as a routine ocular therapeutics evaluation study.
AB - 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. After single instillation of 50 μl 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 sides (eyes) specimens of aqueous humor, cornea, iris, lens, vitreous, conjunctiva, sclera, ciliary body, choroid, retina, optic nerve, optic tract and olfactory bulb were weighed, and blood samples were measured, before combustion in tissue oxidizer and radioactive liquid scintillation counting. Significant 3H-brimonidine levels were found in right and left optic nerves and tracts with extremely low corresponding drug levels in blood. Uveal tract (ciliary body, iris and choroid tissues) brimonidine levels were relatively high in the treated eye, and the highest among contralateral eye tissues. Our data provide the first case of good CNS availability after ocular application of conventional ophthalmic therapeutic agent, through non-systemic routes. Similar neuro-ocular pharmacokinetic studies should be adopted as a routine ocular therapeutics evaluation study.
KW - Brain
KW - Brimonidine
KW - CNS
KW - Ocular
KW - Optic nerves
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=33845548178&partnerID=8YFLogxK
U2 - 10.1080/10611860600992157
DO - 10.1080/10611860600992157
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C2 - 17162736
AN - SCOPUS:33845548178
SN - 1061-186X
VL - 14
SP - 670
EP - 679
JO - Journal of Drug Targeting
JF - Journal of Drug Targeting
IS - 10
ER -