Xiroudaki Styliani, Ianni Federica, Sabbatini Samuele, Roselletti Elena, Monari Claudia, Sardella Roccaldo, Vecchiarelli Anna, Giovagnoli Stefano
Department of Pharmaceutical Sciences, Via del Liceo 1, 06123 Perugia, Italy.
Department of Medicine, Medical Microbiology Section, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy.
Pharmaceutics. 2021 Jan 10;13(1):85. doi: 10.3390/pharmaceutics13010085.
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.
在本研究中，首次通过对全血中的阿米卡星进行定量，对一种旨在增强阿米卡星对难治性肺部感染作用的新型阿米卡星 - 脱氧胆酸盐疏水盐进行了初步体内评估。在小鼠模型中进行鼻内给药后的药代动力学评估显示，与血液相比，肺部的药物滞留量更高，该盐与游离药物之间无显著差异。重复给药后，两种治疗方法均导致疏水盐的组织损伤不显著且炎症略高。全血分析突出显示，在长达48小时内，阿米卡星在血液成分中的分配比例很高，此前未被报道，而在长达72小时内均可检测到显著的肺部水平。这种新观察结果被认为是两种治疗方法的药代动力学曲线几乎重叠的原因。为克服这一问题，可吸入形式的干粉可能最为合适。此外，如果在人体中得到证实，并考虑到目前阿米卡星气雾剂的每日一次给药方案，这种阿米卡星在体内的持久性可能会带来重要的、有待探索的临床意义。
