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

J Pediatr. 2001 Oct;139(4):572-7. doi: 10.1067/mpd.2001.117785.


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 microg/mL (SD 0.4; range, <0.2 to 1.4 microg/mL). A 300-mg dose produced a mean peak serum C(T) of 0.6 microg/mL (SD 0.5; range, <0.2 to 1.2 microg/mL). These peak values are well below the accepted maximum trough concentration with parenteral dosing (2 microg/mL). The target ELF C(T) was 20 microg/mL, 10-fold greater than the minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from very young patients with CF (2 microg/mL). Mean ELF C(T) was 90 microg/mL (SD 54; range, 16 to 204 microg/mL) and exceeded the target concentration in 11 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / metabolism*
  • Bronchoalveolar Lavage
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Cystic Fibrosis / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Nebulizers and Vaporizers
  • Respiratory Mucosa / metabolism*
  • Tobramycin / administration & dosage*
  • Tobramycin / metabolism*


  • Anti-Bacterial Agents
  • Tobramycin