Amikacin nebulization may be used in mechanically ventilated patients for pneumonia prevention and treatment. Available drug delivery and pharmacokinetic knowledge mainly rely on in vitro data and studies of a limited number of patients. To evaluate pulmonary and systemic pharmacokinetics of nebulized amikacin in mechanically ventilated patients and assess the influence of ventilation and nebulization conditions on drug concentrations in the tracheal aspirate and plasma, this ancillary study of a published randomized trial performed population pharmacokinetic modelling on 498 tracheal aspirates and 602 plasma concentrations following 20 mg/kg amikacin vibrating mesh nebulization among 261 patients. Tracheal aspirate amikacin concentrations were very high but variable between patients (median peak concentration 7269 µg/g, interquartile range 4935–9846 µg/g). The tracheal aspirate concentration declined with a median terminal half-life of 7.6 h (interquartile range 5.3–44.2 h), and no accumulation was observed over three doses. Systemic absorption was marginal (median peak plasma concentration 1.9 mg/L, interquartile range 1.3-3.0 mg/L). Despite differences in ventilation mode, circuit type, humidification, inspiratory flow rate, respiratory rate, and tidal volume, no significant impact on tracheal aspirate and plasma amikacin concentrations was observed. Nebulized amikacin achieved high pulmonary concentrations with minimal systemic exposure. Tracheal aspirate and plasma drug concentration were not significantly influenced by ventilation or nebulization conditions. These findings suggest that strict optimization of nebulization parameters may not be necessary when aiming for tracheobronchial antibiotic inhaled delivery such as to prevent ventilator associated pneumonia.
Grégoire et al. (Thu,) studied this question.