Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis

Objectives: To assess the serum and lower respiratory tract tobramycin concentrations (C-T) produced by a single dose of tobramycin for inhalation delivered by a nebulizer and a compressor in patients with cystic Fibrosis (CF) 6 months to 6 years of age. Study design: We performed a dose escalation study of serum C-T measured before and 0.5, 1, 2, and 4 hours after a single dose of inhaled tobramycin, either 180 mg (10 patients) or 300 mg (19 patients). In a separate group of 12 patients, epithelial lining fluid (ELF) C-T was measured by bronchoalveolar lavage 30 to 45 minutes after a 300-mg dose. Results: A 180-mg dose of inhaled tobramycin produced a mean peak serum C-T of 0.5 mug/mL (SD 0.4; range, <0.2 to 1.4 mug/mL). A 300-mg dose produced a mean peak ser-um C-T of 0.6 mug/mL (SD 0.5; range, <0.2 to 1.2 mug/mL). These peak values are well below the accepted maximum trough concentration with parenteral dosing (2 mug/mL). The target ELF C-T was 20 mug/mL, 10-fold greater than the minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from very young patients with CF (2 mug/mL). Mean ELF C-T was 90 mug/mL (SD 54; range, 16 to 204 mug/mL) and exceeded the target concentration in I I patients. Conclusion: In patients with CF ages 6 months to 6 years, a single 300-mg dose of inhaled tobramycin appears to produce safe peak serum concentrations and drug concentrations in the bactericidal range in the lower respiratory tract.