Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues
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 administrat...
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doaj-b8e365023e3d46d7b059b2d91e351c232021-01-11T00:00:39ZengMDPI AGPharmaceutics1999-49232021-01-0113858510.3390/pharmaceutics13010085Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and TissuesStyliani Xiroudaki0Federica Ianni1Samuele Sabbatini2Elena Roselletti3Claudia Monari4Roccaldo Sardella5Anna Vecchiarelli6Stefano Giovagnoli7Department of Pharmaceutical Sciences, Via del Liceo 1, 06123 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via del Liceo 1, 06123 Perugia, ItalyDepartment of Medicine, Medical Microbiology Section, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, ItalyDepartment of Medicine, Medical Microbiology Section, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, ItalyDepartment of Medicine, Medical Microbiology Section, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via del Liceo 1, 06123 Perugia, ItalyDepartment of Medicine, Medical Microbiology Section, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via del Liceo 1, 06123 Perugia, ItalyIn 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.https://www.mdpi.com/1999-4923/13/1/85amikacinamikacin-deoxycholate hydrophobic saltpulmonary deliverypharmacokineticsinflammationamikacin partition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Styliani Xiroudaki Federica Ianni Samuele Sabbatini Elena Roselletti Claudia Monari Roccaldo Sardella Anna Vecchiarelli Stefano Giovagnoli |
spellingShingle |
Styliani Xiroudaki Federica Ianni Samuele Sabbatini Elena Roselletti Claudia Monari Roccaldo Sardella Anna Vecchiarelli Stefano Giovagnoli Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues Pharmaceutics amikacin amikacin-deoxycholate hydrophobic salt pulmonary delivery pharmacokinetics inflammation amikacin partition |
author_facet |
Styliani Xiroudaki Federica Ianni Samuele Sabbatini Elena Roselletti Claudia Monari Roccaldo Sardella Anna Vecchiarelli Stefano Giovagnoli |
author_sort |
Styliani Xiroudaki |
title |
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues |
title_short |
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues |
title_full |
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues |
title_fullStr |
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues |
title_full_unstemmed |
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues |
title_sort |
initial in vivo evaluation of a novel amikacin-deoxycholate hydrophobic salt delivers new insights on amikacin partition in blood and tissues |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-01-01 |
description |
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. |
topic |
amikacin amikacin-deoxycholate hydrophobic salt pulmonary delivery pharmacokinetics inflammation amikacin partition |
url |
https://www.mdpi.com/1999-4923/13/1/85 |
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