Evaluation of serum concentrations achieved with an empiric once-daily tobramycin dosage regimen in children and adults with cystic fibrosis.

objectivesTo assess the ability of an empiric once-daily dosing (ODD) tobramycin regimen to achieve desired serum concentrations in patients with cystic fibrosis (CF); to determine an optimal dosage regimen, using pharmacodynamic parameters; and to evaluate clinical response, adverse effects, and patient/parent satisfaction with ODD.

methodsThis was a prospective single-center trial in patients with CF who are 5 years of age and older requiring intravenous antibiotics. Tobramycin, 10 mg/kg every 24 hours, was infused over 60 minutes, and two serum concentrations were analyzed using 1-compartment pharmacokinetic modeling. Simulations were performed to identify dosage regimens that maximized desired pharmacodynamic parameters. Other data included demographics, symptoms, spirometry, adverse events, and satisfaction with ODD.

resultsA total of 14 children and 11 adults completed the study. Empiric doses resulted in mean peak tobramycin concentrations of 28.7 ± 5.5 mg/L and undetectable trough concentrations. Only 42% of patients achieved desired peak serum concentrations (20-30 mg/L) with the empiric regimen. A regimen of 12 mg/kg every 24 hours would achieve modified pharmacodynamic goals with an acceptable peak range of 20 to 35 mg/L. Forced expiratory volume in 1 second improved in 15 of 20 (75%) patients with ODD. Two patients experienced reversible vestibular adverse effects attributed to tobramycin. All patients were satisfied or very satisfied with ODD because of convenience and ease of use.

conclusionsAn empiric tobramycin regimen of 10 mg/kg every 24 hours did not achieve desired serum concentrations for most patients, although all patients demonstrated clinical improvement. Desired tobramycin concentrations with modified pharmacodynamic goals could be achieved by using an empiric dosage of 12 mg/kg every 24 hours. Prospective evaluation of this regimen with individualized patient monitoring is needed to ensure safety and efficacy and to monitor the effects on microbial resistance patterns.