Background: Jet nebulizers coupled to spacers are frequently used to promote drug lung deposition, but their clinical efficacy has not been established. Few in vivo studies have been performed with mesh nebulizers, commonly used to nebulize antibiotics. Our study compared inhaled mass and urinary drug concentration of amikacin by using three different nebulizer delivery configuration systems: a standard unvented jet nebulizer (Sidestream(®)) used alone or coupled to a 110-mL corrugated piece of tubing and a vibrating mesh nebulizer (e-Flow rapid(®)).
Method: The inhaled mass of amikacin was assessed using the residual gravimetric method. Delivery efficacy was evaluated by assessing amikacin urinary drug concentration in six healthy spontaneously breathing volunteers. Urinary amikacin was monitored by fluorescent polarization immunoassay then cumulative excreted amount and antibiotic elimination rate were calculated.
Results and conclusions: The total daily amount of amikacin urinary excretion (Cu) was almost twice as high with eFlow rapid(®) compared to Sidestream(®) used alone; intermediate values being observed when the device was coupled to a corrugated piece of tubing. The latter configuration was also associated with a higher total daily amount of amikacin urinary excretion. In vivo drug output rate was around threefold higher with the eFlow Rapid(®) than with the Sidestream(®) used in any configuration. These results were concordant to those obtained with in vitro analysis comparing inhaled mass of amikacin for the three nebulizers. The elimination constant (Ke) and the mass median aerodynamic diameter (MMAD) did not differ between the three devices. In conclusion, the vibrating mesh nebulizer is more efficient, promoting larger urinary drug concentration and drug output. Coupling a corrugated piece of tubing to the standard jet nebulizer favors delivery efficacy.