1 Novartis Institutes for BioMedical Research, Emeryville, CA, USA.
2 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
SLAS Discov. 2017 Dec;22(10):1239-1245. doi: 10.1177/2472555217724780. Epub 2017 Aug 8.
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is becoming an important technology to determine the distribution of drugs and their metabolites in the tissue of preclinical species after dosing. Interest in IMS is growing in the ophthalmology field, but little work to this point has been done to investigate ocular drug transit using this technology. Information on where and how a drug is distributing through the eye is important in understanding efficacy and whether it is reaching the desired target tissue. For this study, ocular distribution of brimonidine was investigated in rabbits following topical administration. Brimonidine has been shown to lower intraocular pressure and is approved to treat glaucoma, the second leading cause of blindness in the world. We have developed IMS methods to assess transit of topically administered brimonidine from the anterior to the posterior segment of rabbit eyes. Using IMS, brimonidine was detected in the cornea, aqueous humor, iris, and posterior segments of the eye. The distribution of brimonidine suggests that the route of transit following topical administration is mainly through the uvea-scleral route. This study demonstrates that IMS can be applied to assess ocular transit and distribution of topically administered drugs.
基质辅助激光解吸/电离成像质谱（MALDI IMS）正在成为一种重要的技术，用于确定给药后临床前物种组织中药物及其代谢物的分布。在眼科领域，人们对 IMS 的兴趣日益浓厚，但迄今为止，很少有研究利用这项技术来研究眼部药物转运。了解药物在眼部的分布位置和方式对于评估药物的疗效以及药物是否到达预期的靶组织非常重要。在这项研究中，我们研究了局部给予后兔子眼中布美他尼的分布情况。布美他尼已被证明可降低眼内压，用于治疗青光眼，这是全球第二大致盲原因。我们已经开发了 IMS 方法来评估局部给予的布美他尼从前节到后节的转运情况。通过 IMS，我们在角膜、房水、虹膜和眼睛的后节中检测到了布美他尼。布美他尼的分布表明，局部给药后的转运途径主要是通过葡萄膜巩膜途径。这项研究表明，IMS 可用于评估局部给予药物的眼部转运和分布。
