title: The influence of breathing mode on tobramycin serum levels using the I-neb AAD system in adults with cystic fibrosis.
abstract: BACKGROUND
  The clinical effectiveness of inhaled tobramycin depends on the dose reaching the desired regions of the lungs. This study evaluates the influence of breathing mode on tobramycin lung deposition using its pharmacokinetics as surrogate for deposition.
  
  
  METHODS
  In a randomized, open-label, crossover study lung deposition in 18 adult CF patients is evaluated following inhalation of tobramycin aerosol using the I-neb nebulizer with TBM (Tidal Breathing Mode) and TIM (Target Inhalation Mode) breathing patterns. Breathing in TIM forced the patient to inhale in a slow and deep manner. Patients were categorized in three subgroups according to their lung function: ≤59%, 60-79% or ≥80% of FEV1 predicted. Blood samples were collected in order to model tobramycin pharmacokinetics. Nebulization time was recorded.
  
  
  RESULTS
  Inhalation with TIM resulted in significantly higher maximum serum levels and area under the concentration-time curves (0-24h). Mean bioavailability of TIM relative to TBM was 1.53±0.41. Mean nebulization time was reduced by half with TIM. Subgroup category did not affect the results.
  
  
  CONCLUSIONS
  Slow and deep inhalation of aerosolized tobramycin resulted in higher lung deposition and shorter nebulization time compared to tidal breathing, regardless of the disease severity of the CF patient. Dutch trial register number NTR3109.
authors: Central Hospital Pharmacy, The Hague, The Netherlands; Department of Clinical Pharmacology, Haga Teaching Hospital, The Hague, The Netherlands. Electronic address: a.vanvelzen@hagaziekenhuis.nl.
authors: A J
authors: AJ
authors: van Velzen
authors: Central Hospital Pharmacy, The Hague, The Netherlands; Department of Clinical Pharmacology, Haga Teaching Hospital, The Hague, The Netherlands.
authors: J W F
authors: JW
authors: Uges
authors: Central Hospital Pharmacy, The Hague, The Netherlands; Department of Clinical Pharmacology, Haga Teaching Hospital, The Hague, The Netherlands.
authors: P P H
authors: PP
authors: Le Brun
authors: Central Hospital Pharmacy, The Hague, The Netherlands.
authors: P
authors: P
authors: Shahbabai
authors: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors: D J
authors: DJ
authors: Touw
authors: Department of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands.
authors: H G M
authors: HG
authors: Heijerman
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012119:Respiration; D014031:Tobramycin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin
keywords: Aerosol; Breathing mode; Inhalation; Lung deposition; Pharmacokinetics; Tobramycin