Abdulrazik Muhammad, Tamilvanan Shunmugaperumal, Benita Simon
Pharmaceutics Department, School of Pharmacy, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem, 91120, Israel.
J Drug Target. 2006 Dec;14(10):670-9. doi: 10.1080/10611860600992157.
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 microl 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.
迄今为止，局部应用的眼科治疗药物出现中枢神经系统（CNS）副作用的风险被认为是这些药物全身吸收的结果。本文设想了眼部应用后通过非全身途径将药物递送至中枢神经系统的可能性。在右眼结膜囊单次滴注50微升3H放射性标记的阿法根溶液（0.2%）后，在每个时间点（5、15、30和60分钟）处死3只雄性白化兔（2-2.5千克）。在组织氧化器中燃烧并进行放射性液体闪烁计数之前，对房水、角膜、虹膜、晶状体、玻璃体、结膜、巩膜、睫状体、脉络膜、视网膜、视神经、视束和嗅球的双侧（双眼）标本进行称重，并检测血样。在左右视神经和视束中发现了显著的3H溴莫尼定水平，而血液中的相应药物水平极低。在治疗眼的葡萄膜（睫状体、虹膜和脉络膜组织）中溴莫尼定水平相对较高，且在对侧眼组织中最高。我们的数据首次证明了常规眼科治疗药物经眼部应用后通过非全身途径具有良好的中枢神经系统可达性。类似的神经眼药代动力学研究应作为常规的眼部治疗评估研究采用。
