Pharmacokinetics and safety of once daily double dose inhaled tobramycin administered with the controlledinhalation AKITA® and conventional PARI-LC® Plus nebulizer in cystic fibrosis

摘要

Objectives: Better treatment outcomes in cystic fibrosis (CF) may be expected by changing standard twice daily tobramycin inhalation with the conventional PARI-LC® Plus nebulizer to once daily inhalation of the double dose with the controlled-inhalation AKITA® nebulizer. We aimed to determine pharmacokinetics (PK) and safety of once daily inhalation of the double recommended tobramycin dose with the AKITA® in patients with CF. Systemic absorption can be used as surrogate for safety. Methods: In a randomized open-label crossover study, PK of inhaled tobramycin in 10 adult CF patients was assessed following inhalation of the double recommended dose with the AKITA® (300 mg fill dose) and PARI-LC® Plus (600 mg fill dose). Blood samples were drawn until 24 hours after inhalation. Results: No significant differences were found in the maximum and trough serum levels, time to maximum level and area under the curve (0-24 hours). Both maximum and trough levels were well below their toxic limits for both nebulizers and for all patients. Both inhalations were well tolerated and no serious adverse events occurred. Nebulization time was 33% shorter with AKITA®. Conclusion: Once daily inhalation of the double tobramycin dose with the controlled-inhalation AKITA® nebulizer resulted in safe serum levels, with comparable systemic exposure to once daily PARI-LC® Plus inhalation and higher peak levels compared to the standard twice daily dosing regimen. Shorter nebulization time with the AKITA® could reduce treatment burden. The efficacy of once daily tobramycin inhalation on CF lung infection will be further investigated.