title: Sputum tobramycin concentrations in cystic fibrosis patients with repeated administration of inhaled tobramycin.
abstract: BACKGROUND
  Dosing of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients was based on single-dose pharmacokinetic studies. This investigation was prompted by evidence of possible antibiotic accumulation in respiratory secretions with repeated dosing. The objectives were to evaluate whether tobramycin accumulates in respiratory secretions with repeated inhalation, compare total and biologically active tobramycin concentrations in CF sputum, and evaluate sputum induction for obtaining secretions for drug concentration assay.
  
  
  METHODS
  Individuals with CF ≥10 years of age were enrolled at the beginning of a course of TSI, 300 mg twice daily for 28 days. Two study visits were conducted, 1-2 days and 24-28 days after initiation of TSI treatment. Induced sputum and expectorated sputum samples were collected for measurement of trough and peak tobramycin concentrations at each visit. Total tobramycin concentrations were measured by high-pressure liquid chromatography and bioactive concentrations by bioassay.
  
  
  RESULTS
  Twenty participants completed the study. Trough concentrations were similar at visits 1 and 2, as were peak concentrations. Trough bioactive and total tobramycin concentrations were similar (mean ratio 1.2, 95% CI 0.56, 1.87), but peak bioactive concentrations were significantly lower than peak total concentrations (mean ratio 0.33, 95% CI 0.23, 0.44). Sputum induction was well tolerated.
  
  
  CONCLUSIONS
  No evidence of significant drug accumulation in respiratory secretions with repeat dosing of TSI was seen. Peak bioactive concentrations, although lower than peak total concentrations, were still generally well within the bactericidal range. Sputum induction as a method for determining airway drug concentrations appears safe and feasible.
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, WA 98105, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ruddy
authors.forename: Julia
authors.initials: J
authors.lastname: Emerson
authors.forename: Richard
authors.initials: R
authors.lastname: Moss
authors.forename: Alan
authors.initials: A
authors.lastname: Genatossio
authors.forename: Sharon
authors.initials: S
authors.lastname: McNamara
authors.forename: Jane L
authors.initials: JL
authors.lastname: Burns
authors.forename: Gail
authors.initials: G
authors.lastname: Anderson
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D010865:Pilot Projects; D013183:Sputum / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin