Intensive Care Medicine

, Volume 34, Issue 4, pp 755–762

Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated healthy subjects

  • Stephan Ehrmann
  • Emmanuelle Mercier
  • Laurent Vecellio
  • David Ternant
  • Gilles Paintaud
  • Pierre-François Dequin
Experimental

DOI: 10.1007/s00134-007-0935-1

Cite this article as:
Ehrmann, S., Mercier, E., Vecellio, L. et al. Intensive Care Med (2008) 34: 755. doi:10.1007/s00134-007-0935-1

Abstract

Objective

Nebulized amikacin may be an attractive option for the treatment of lung infections. Low systemic absorption may permit the use of high doses, leading to high lung concentrations without systemic toxicity. We evaluated the pharmacokinetics and safety of an optimized high-dose amikacin nebulization technique.

Design

in vitro and in vivo pharmacokinetic study.

Patients and participants

Six healthy volunteers (age 21–30 years, weight 49–68 kg).

Interventions

The Aeroneb Pro nebulizer with an Idehaler vertical spacer was evaluated in a bench study. Amikacin was administered intravenously (15 mg/kg) and nebulized (40, 50, and 60 mg/kg) during noninvasive pressure-support ventilation through a mouthpiece.

Measurements and results

Median (interquartile range) in vitro inhaled fraction was 31% (30–32) and inhalable output was 681 mg/h (630–743). Serum concentrations after nebulization were less than or equal to those after infusion. The area under the serum concentration curve was significantly higher after infusion (138 mg h–1l–1, 122–143) than after nebulization (49 mg h–1l–1, 39–55, at 40 mg/kg; 63, 53–67 at 50; 66, 50–71, at 60). Peak serum concentration was also higher after infusion: 48 mg/l (45–49) after infusion compared to 8.2 (5.6–8.7), 9.2 (7.6–10.2), and 9.2 (5.2–10.3), respectively. Mean absorption times after nebulization were 2 h 24 min (2,07–2,45), 2 h 21 min (2,07–2,35), and 2 h 5 min (2,00–2,25), respectively. No side effect was observed.

Conclusions

Nebulization of up to 60 mg/kg amikacin appears to be safe in healthy subjects and associated with lower serum concentrations than a 15 mg/kg infusion.

Keywords

Administration, aerosolRespiration, artificialDrug evaluation

Supplementary material

134_2007_935_MOESM1_ESM.avi (3.3 mb)
Electronic Supplementary Material (AVI 3,4M)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Stephan Ehrmann
    • 1
  • Emmanuelle Mercier
    • 1
  • Laurent Vecellio
    • 2
  • David Ternant
    • 3
  • Gilles Paintaud
    • 3
  • Pierre-François Dequin
    • 1
  1. 1.Service de réanimation médicale polyvalenteCentre hospitalier universitaire de ToursTours cedex 9France
  2. 2.INSERM U-618, IFR 135Université François Rabelais, Faculté de médecineTours cedexFrance
  3. 3.Université François Rabelais Tours, EA 3853, IFR 135Centre hospitalier universitaire de Tours, Laboratoire de Pharmacologie-ToxicologieTours cedex 9France