A comparison of systemic and local dexamethasone administration: From perilymph/cochlea concentration to cochlear distribution

Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and ′immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs. (C) 2018 The Authors. Published by Elsevier B.V.