TY - JOUR
T1 - Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin in Children with Cystic Fibrosis
AU - Akkerman-Nijland, Anne M
AU - Hagedoorn, Paul
AU - Rottier, Bart L
AU - Grasmeijer, Floris
AU - Frijlink, Henderik Erik W
AU - van Luin, Mathijs
AU - Ter Weijden, E
AU - Merkus, Peter J
AU - Touw, Daan J
AU - Akkerman, Onno W
AU - Koppelman, Gerard H
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/3/7
Y1 - 2025/3/7
N2 - Background:Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in persons with Cystic Fibrosis (CF). Nebulization with tobramycin or colistin is mostly applied but has a significant treatment burden. Dry powder (DP) inhalation may offer an attractive alternative. The aim of this study was to assess local tolerability and the systemic pharmacokinetic parameters of increasing doses of dry powder tobramycin. Methods: This was a local tolerability and pharmacokinetic evaluation pilot study DP tobramycin of three different doses inhaled through the Cyclops (30, 60, 120 mg) in ten persons with CF, aged 6-18 years, compared to nebulization of tobramycin solution. Results: Both nebulization of tobramycin in solution and inhalation of dry powder tobramycin were well tolerated. None of the participants showed a significant drop in FEV1 after inhalation. The only two adverse events were cough and bad taste in, respectively, 20% and 13% of all inhalations, compared to 10% cough and 60% bad taste with nebulization. Systemic tobramycin levels were not detected after 30 mg, detected only in 10% after 60 mg and in 30% after 120 mg, compared to 80% after nebulization. Conclusions: Inhalation of dry powder tobramycin using the Cyclops is well tolerated, with no significant drop in FEV1, and only mild adverse events of cough and bad taste. We found only a few detectable systemic tobramycin levels after inhalation of dry powder tobramycin. We recommend that future studies should focus on the relation between dose and inhaler resistance in different pediatric age groups.
AB - Background:Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in persons with Cystic Fibrosis (CF). Nebulization with tobramycin or colistin is mostly applied but has a significant treatment burden. Dry powder (DP) inhalation may offer an attractive alternative. The aim of this study was to assess local tolerability and the systemic pharmacokinetic parameters of increasing doses of dry powder tobramycin. Methods: This was a local tolerability and pharmacokinetic evaluation pilot study DP tobramycin of three different doses inhaled through the Cyclops (30, 60, 120 mg) in ten persons with CF, aged 6-18 years, compared to nebulization of tobramycin solution. Results: Both nebulization of tobramycin in solution and inhalation of dry powder tobramycin were well tolerated. None of the participants showed a significant drop in FEV1 after inhalation. The only two adverse events were cough and bad taste in, respectively, 20% and 13% of all inhalations, compared to 10% cough and 60% bad taste with nebulization. Systemic tobramycin levels were not detected after 30 mg, detected only in 10% after 60 mg and in 30% after 120 mg, compared to 80% after nebulization. Conclusions: Inhalation of dry powder tobramycin using the Cyclops is well tolerated, with no significant drop in FEV1, and only mild adverse events of cough and bad taste. We found only a few detectable systemic tobramycin levels after inhalation of dry powder tobramycin. We recommend that future studies should focus on the relation between dose and inhaler resistance in different pediatric age groups.
U2 - 10.3390/pharmaceutics17030347
DO - 10.3390/pharmaceutics17030347
M3 - Article
C2 - 40143011
SN - 1999-4923
VL - 17
JO - Pharmaceutics
JF - Pharmaceutics
IS - 3
M1 - 347
ER -