RESUMO
STUDY OBJECTIVES: 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. DESIGN: 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. SETTING: Medical school-affiliated teaching hospital. PATIENTS: 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). INTERVENTIONS: None. MAIN 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.