Tobramycin nebulization with I-neb® in children with cystic fibrosis (TONI study): Pharmacokinetics and safety

Objectives: Usage of the efficient, small, silent and rapid I-neb® nebulizer can reduce treatment burden in patients with cystic fibrosis (CF). Limited information is available for use in children, especially regarding the correct dosage and safety of potentially toxic antibiotics. We aimed to determine pharmacokinetics (PK) and safety of tobramycin inhalation solution (TIS) with the I-neb® compared to the standard PARI-LC® Plus nebulizer in children with CF. Methods: In two separate study visits (cross-over) blood samples of 22 children aged 6-18 years were collected for PK analysis following TIS nebulization with the I-neb® (75 mg) and PARI-LC® Plus (300 mg) nebulizer. Study visits were separated by one month, in which one of the study nebulizers was used twice daily (randomized). Renal and hearing tests were performed on both study visits to test for aminoglycoside toxicity. Adverse events were monitored. Results: (preliminary results of 16 patients): Safe serum levels were reached with no significant differences in PK parameters between nebulizers. Maximum serum level (mg/L), time to maximum serum level (h), trough serum level 12 h (mg/L) and area under the curve 0-24 h (h.mg/L) were 1.96±1.41, 1.02±0.48, 0.20±0.08 and 12.78±7.33 for the I-neb® and 1.44±0.99, 1.05±0.51, 0.18±0.11 and 10.28±5.16 for the PARI-LC® Plus, respectively. There was no impairment in renal or hearing function and inhalations were well tolerated. Conclusion: Nebulization of 75 mg TIS with the I-neb® in children with CF was safe and resulted in comparable systemic exposure to 300 mg TIS with the PARI-LC® Plus.