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. 2020 Jan 16:10:1562.
doi: 10.3389/fphar.2019.01562. eCollection 2019.

Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model

Fabien Espitalier  1   2 , François Darrouzain  3   4 , Jean-Michel Escoffre  1 , David Ternant  3   4 , Eric Piver  5 , Ayache Bouakaz  1 , Francis Remerand  1   2
Affiliations

Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model

Fabien Espitalier et al. Front Pharmacol. .

Abstract

The poor diffusion of intravenous antibiotics in lung tissue makes nosocomial pneumonia challenging to treat, notably in critical patients under mechanical ventilation. The combination of ultrasound and microbubbles (USMB) is an emerging method for non-invasive and targeted enhancement of uptake of various drugs in several organs. This study aims to evaluate if USMB may increase amikacin concentration in condensed lung tissues in a mechanically ventilated rabbit model. When applied 60 or 160 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the condensed lung tissue by 1.33 (p = 0.025) or 1.56-fold (p = 0.028) respectively. When applied 70 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the muscle tissue by 2.52 (p = 0.025). In conclusion, this study demonstrates that USMB is a promising method for the targeted delivery of amikacin in mechanically ventilated condensed lung, thus opening new therapeutic fields against lung infections.

Keywords: amikacin; antibiotic therapy; lung; microbubbles; sonoporation; ultrasound.

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Figures

Figure 1
Figure 1
Study design with high (A) and low (B) amikacin concentrations.
Figure 2
Figure 2
Amikacin pharmacokinetics (PKs) in mechanically ventilated anesthetized rabbits (N = 11 rabbits). T0 was set as the beginning of intravenous (iv) amikacin infusion (15 mg/kg over 30 min).
Figure 3
Figure 3
Boxplots of amikacin concentration in lung and muscle tissues (N = 7–8 rabbits/condition; each rabbit was its own control). Green arrows indicate on the PKs curve the amikacin blood concentration at the time of sonoporation.
See this image and copyright information in PMC

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