In this study, an initial in vivo evaluation of a new amikacin-deoxycholate hydrophobic salt aimed at potentiating amikacin action against hard-to-treat lung infections was undertaken by quantifying, for the first time, amikacin in whole blood. Pharmacokinetic evaluation after intranasal administration in a murine model showed higher drug retention in the lungs compared to blood, with no significant differences between the salt and the free drug. Upon repeated administrations, the two treatments resulted in nonsignificant tissue damage and mild higher inflammation for the hydrophobic salt. Whole-blood analysis highlighted an unreported high partition of amikacin in blood components up to 48 h, while significant lung levels were measured up to 72 h. Such a new observation was considered responsible for the nearly overlapping pharmacokinetic profiles of the two treatments. To overcome such an issue, a dry powder in an inhalable form may be best suited. Moreover, if confirmed in humans, and considering the current once-a-day regimen for amikacin aerosols, important yet-to-be-explored clinical implications may be postulated for such amikacin persistence in the organism.

中文翻译：

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新型阿米卡星-脱氧胆酸盐疏水盐的体内初步评价提供了对阿米卡星在血液和组织中分配的新见解

在这项研究中，首次通过对全血中的阿米卡星进行定量，对旨在增强阿米卡星对难于治疗的肺部感染的作用的新型阿米卡星-脱氧胆酸盐疏水盐进行了体内初步评估。鼻腔给药在鼠模型中进行的药代动力学评估显示，与血液相比，肺中的药物保留更高，盐和游离药物之间无显着差异。重复给药后，两种治疗方法均导致组织无明显损伤，疏水性盐的炎症程度略高。全血分析显示，长达48小时的血液成分中未报告的丁胺卡那霉素高分配，而长达72小时的肺水平显着升高。这种新的观察结果被认为是两种治疗方法几乎重叠的药代动力学特征的原因。为了克服这个问题，可吸入形式的干粉可能是最合适的。此外，如果在人体中得到证实，并考虑到目前每天使用阿米卡星气雾剂的方案，则可以推测这种阿米卡星在生物体内的持久性具有重要的尚未探索的临床意义。