title: Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation.
abstract: OBJECTIVE
  To compare the pharmacokinetics (PK) of tobramycin in patients with cystic fibrosis (CF) before and after bilateral lung transplantation, in order to evaluate optimal dosing practices post transplant.
  
  
  METHODS
  Retrospective, single-center, chart review study, in which tobramycin concentrations from CF patients were used to calculate PK parameters, including elimination rate constant, half-life, volume of distribution (Vd), area under the curve (AUC), and clearance before and after lung transplantation.
  
  
  METHODS
  Medical school-affiliated teaching hospital.
  
  
  METHODS
  Eight patients with CF, who received a bilateral lung transplant from January 1, 2005 through August 1, 2009 (4 males, 4 females; mean age 26.3 years).
  
  
  METHODS
  None.
  
  
  RESULTS
  Sixty-nine sets of pre- (n=52) and post transplant (n=17) tobramycin concentrations were available. PK parameters were significantly altered post transplant. Elimination rate constant decreased 38% from 0.26±0.1 to 0.16±0.1 h(-1) (P<0.001), with a related increase of 200% in half-life from 2.8±0.8 to 8.4±8.7 h (P<0.001). Clearance decreased 25% post transplant from 67.3±32.3 to 50.2±15.9 mL/min (P=0.04). No statistically significant change occurred in AUC or Vd after transplant, although a trend was seen toward increased Vd. Dosage requirements after transplantation were significantly lower, 10.7±2.5 and 7.6±1.6 mg/kg/day, pre and post transplant, respectively (P<0.001). Concentrations were also evaluated in 2 time periods: 0-3 weeks and ≥6 weeks post transplant, based on available data. Clearance and Vd ≥6 weeks post transplant did not significantly differ from pre-transplant values (P=0.28 and 0.54, respectively), suggesting that these changes may be temporary.
  
  
  CONCLUSIONS
  The results suggest that tobramycin PK are altered in patients with CF after bilateral lung transplantation, although no clear trend was seen owing to inter-patient variability. We propose that PK parameters should be reassessed during each treatment course post transplant.
authors.affiliation: UK HealthCare Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Walsh
authors.forename: G A
authors.initials: GA
authors.lastname: Davis
authors.forename: D
authors.initials: D
authors.lastname: Hayes
authors.forename: R J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: K A
authors.initials: KA
authors.lastname: Weant
authors.forename: J D
authors.initials: JD
authors.lastname: Flynn
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000601:surgery*; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D012189:Retrospective Studies; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin