title: Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pulmonary Medicine, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: R
authors.initials: R
authors.lastname: Gibson
authors.forename: S
authors.initials: S
authors.lastname: McNamara
authors.forename: J
authors.initials: J
authors.lastname: Emerson
authors.forename: K S
authors.initials: KS
authors.lastname: McCoyd
authors.forename: R
authors.initials: R
authors.lastname: Shell
authors.forename: D
authors.initials: D
authors.lastname: Borowitz
authors.forename: M W
authors.initials: MW
authors.lastname: Konstan
authors.forename: G
authors.initials: G
authors.lastname: Retsch-Bogart
authors.forename: R W
authors.initials: RW
authors.lastname: Wilmott
authors.forename: J L
authors.initials: JL
authors.lastname: Burns
authors.forename: P
authors.initials: P
authors.lastname: Vicini
authors.forename: A B
authors.initials: AB
authors.lastname: Montgomery
authors.forename: B
authors.initials: B
authors.lastname: Ramsey
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009330:Nebulizers and Vaporizers; D020545:Respiratory Mucosa / Q000378:metabolism*; D014031:Tobramycin / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin