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


METHODS
in vitro and in vivo pharmacokinetic study.


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


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


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(-1)l(-1), 122-143) than after nebulization (49 mg h(-1)l(-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.
Service de réanimation médicale polyvalente, Centre hospitalier universitaire de Tours, 37044, Tours cedex 9, France. stephanehrmann@gmail.com
Stephan
S
Ehrmann
Emmanuelle
E
Mercier
Laurent
L
Vecellio
David
D
Ternant
Gilles
G
Paintaud
Pierre-François
PF
Dequin
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000583:Amikacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male
D000336:Aerosols; D000900:Anti-Bacterial Agents; D000583:Amikacin