Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation

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.