Pharmacokinetics and tolerability of once daily double dose tobramycin inhalation in cystic fibrosis using controlled and conventional nebulization: comparison between PARI-LC Plus and AKITA nebulizer OBJECTIVE 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. DESIGN and METHODS In a randomized open-label crossover pilot 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. Inhalation with both nebulizers was well tolerated. Nebulization time was significantly shortened, less side effects were reported and a higher degree of satisfaction was attained with the AKITA nebulizer.
|Publication status||Published - 12 Apr 2019|
van Velzen, A. J., Bos, A. C., Touw, D. J., Tiddens, H. A. W. M., Heijermane, H. G. M., & Janssens, H. M. (2019). Farmacokinetiek en tolerantie van eenmaal daagse verneveling van de dubbele dosis tobramycine bij cystische fibrose: Vergelijking tussen PARI-LC Plus- en AKITA-vernevelaar. Pharmaceutisch Weekblad, 154(15), 25-28.