PHARMACOKINETICS AND SAFETY OF TOBRAMYCIN AFTER ONCE-DAILY ADMINISTRATION IN PATIENTS WITH CYSTIC-FIBROSIS

Study objective: Tobramycin is commonly used to treat respiratory trac t infections in patients with cystic fibrosis, We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobr amycin in this population, Design: Multiple blood samples were collect ed from each patient, and serum concentrations of tobramycin were dete rmined by a fluorescence polarization immunoassay, Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audi ometric evaluations were performed at the start and end of therapy. Me asurements and results: Eighteen patients (mean age, 24.6 years) recei ved tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion o ver 20 min, The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L, A mean dose of 11.9+/-1.9 mg/kg was needed to obtai n a theoretical mean peak serum concentration of 42.4+4.5 mg/L, The me an total body clearance, apparent volume of distribution, and eliminat ion half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively, The period of time that the serum concentration exce eded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer com pared with the use of divided daily closes in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. Conclusion: Based on our data, tobra mycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.