Characterization on the Bench of an Amikacin Aerosol Before Clinical Studies

ABSTRACT

It has been suggested that nebulized antipseudomonas therapy may be of benefit in cystic fibrosis (CF) patients. Amikacin is effective against Pseudomonas aeruginosa and does not contain sulfites. As a prelude to clinical studies that will use gamma camera techniques to quantify amikacin aerosol deposition, we present the characteristics of the amikacin aerosol and demonstrate that labeling it does not change its dynamics. Human serum albumin (HSA) was labeled with ^99mTc and was added to an amikacin solution (1 g per 8 mL and 1.5 g per 12 mL). Amikacin mixed with this tracer was charged in an ultrasonic nebulizer (Syst'Am LS; Villeneuve sur Lot, France). Low-resistance filters were connected between the nebulizer mouthpiece and a piston pump. The filters were changed after each 3-minute period during the 18-minute nebulization process. The mass of radiolabeled amikacin collected from each filter was measured by fluorescence polarization immunoassay (FPIA) and estimated from ^99mTc countings. Particle size distribution, mass median aerodynamic diameter (MMAD), and geometric standard deviation σg) of the un labeled and radiolabeled aerosols were measured by inserting a 10-stage cascade impactor between the nebulizer and the piston pump. The mass of amikacin that impacted on each stage was measured by FPIA for both unlabeled and radiolabeled aerosols. There was a close correlation between FPIA and ^99mTc countings to measure the mass of radiolabeled amikacin deposited on filters (y = 1.32 x − 1.91, r = 0.97, P < 0.0001). Maximum inhaled mass reached 30% of the nebulizer charge with the 1 g per 8 mL solution and 55% with the 1.5 g per 12 mL solution. There was also a close correlation between distribution of the unlabeled and radiolabeled aerosols (y = 0.92 x + 0.74, r = 0.95, P < 0.0001). MMAD (σg) was 3.0 (1.7) μm. We conclude that it is possible to produce an aerosol of amikacin that may deposit peripherally in the lungs. Labeling the drug does not alter the dynamic characteristics of the aerosol.