Although combination of oral and transtympanic drug therapy (CT) has been proved more effective and safer for idiopathic sudden sensorineural hearing loss (ISSNHL) by some clinical trials, there are few laboratory researches on the pharmacokinetics in the inner ear following CT on account of structural limitations of the inner ear. The aim of the present study was to investigate the pharmacokinetic behaviors of CT in the inner ear of mice. Eighteen transgenic GFAP-Luc mice which express luciferase in cochlear spiral ganglion cells were divided into oral administration (OR) group, transtympanic injection route (TT) group and CT group, and luciferin was delivered into the inner ear of these mice through oral, transtympanic or combined routes, respectively. A new in vivo imaging system was used to observe luciferin/luciferase signals and the compare the pharmacokinetics of different administration routes in the inner ear of mice. Bioluminescence signals were observed in the inner ear 3.3 ± 2.6 min after CT, significantly earlier than that of OR group (15.8 ± 7.4 min). CT owned the longest reaching-peak time and largest area under the curve (AUC) among three groups. Compared to TT, CT had longer biological half-life and higher AUC value, but did not displayed stronger peak value. There were significant differences in the peak values between OR group and TT group and between OR group and CT group. This study suggests that the OR route is less effective than the TT or CT route, and combination of OR and TT can deliver more drugs into the inner ear and confer a longer therapeutic window, but cannot increase drug intensity.

中文翻译：

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口服、经鼓室给药和联合给药后内耳中药物可用性的比较。

尽管一些临床试验证明口服和经鼓室药物治疗（CT）联合治疗特发性突发感音神经性听力损失（ISSNHL）更有效、更安全，但由于结构性原因，很少有实验室研究 CT 后内耳的药代动力学。内耳的局限性。本研究的目的是研究 CT 在小鼠内耳中的药代动力学行为。将 18 只在耳蜗螺旋神经节细胞中表达荧光素酶的转基因 GFAP-Luc 小鼠分为口服给药（OR）组、经鼓室注射途径（TT）组和 CT 组，荧光素通过口服、经鼓膜途径递送到这些小鼠的内耳中。或组合路线，分别。一种新的体内成像系统用于观察荧光素/荧光素酶信号，并比较不同给药途径在小鼠内耳中的药代动力学。CT后3.3±2.6分钟内耳观察到生物发光信号，明显早于OR组（15.8±7.4分钟）。CT在三组中具有最长的达峰时间和最大的曲线下面积（AUC）。与TT相比，CT具有更长的生物半衰期和更高的AUC值，但没有表现出更强的峰值。OR组与TT组、OR组与CT组的峰值存在显着差异。这项研究表明，OR 途径不如 TT 或 CT 途径有效，OR 和 TT 的组合可以将更多的药物输送到内耳并赋予更长的治疗窗口，