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首页> 外文期刊>Audiology & neuro-otology >Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs
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Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs

机译：与豚鼠中的中耳应用相比，地塞米松和地塞米松磷酸盐进入漂亮睫毛蛋白酶

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Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear. (C) 2018 S. Karger AG, Basel
机译：磷酸含量广泛用于人类的尿道治疗。当作为地塞米松磷酸盐溶液或微粉化的地塞米松悬浮液给予时，我们将地塞米松进入的药代动力学评估为漂亮的麦克风溶液，在培养基中用猪氧基聚合物凝胶包叠。在对豚鼠的1小时施用后，从每只动物的横向半圆形管中收集10个独立的露晶样品，允许在圆形窗口中进入，并独立评估缝隙。两种形式的地塞米松主要在圆形窗口（73％）处进入漂亮米照片，在镫骨处进入较低的比例（22％）。当通过施用浓度标准化时，根据其计算的脂质溶解度和极性表面积性能，发现磷酸磷酸磷酸盐比不同的地塞米松进入更缓慢的磷酸盐。因此，当用于局部疗法时，磷酸酯的磷酸盐具有有问题的动力学组合。它相对不透水，仅从中耳慢慢进入漂亮的照片。然后将其代谢为耳朵到地塞米松，这通过组织边界更渗透，并且从漂亮的漂泊损失。了解分子特性对漂亮药物分布的影响提供了新的理解水平，这可能有助于优化耳朵的药物疗法。 （c）2018年S. Karger AG，巴塞尔

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