Gentamicin and tobramycin pharmacokinetics in patients with cystic fibrosis.

Abstract

Pharmacokinetic variables were compared in patients with cystic fibrosis receiving gentamicin or tobramycin for the treatment of a pseudomonas pulmonary infection. Sixty-nine pediatric patients receiving gentamicin sulfate (n = 31) or tobramycin sulfate (n = 38) were studied. Doses were administered every six hours. All patients received concurrent ticarcillin therapy, had a mild fever, and normal hematocrit and serum creatinine values. Amino-glycoside pharmacokinetic variables were calculated. Tobramycin and gentamicin serum concentrations were determined by radioimmunoassay. The mean (+/- S.D.) half-lives for the tobramycin and gentamicin patients were 1.2 +/- 0.5 and 1.4 +/- 0.4 hr, respectively. The average volume of distribution and clearance values for the tobramycin and gentamicin patients were 0.33 +/- 0.20 liters/kg and 2.98 +/- 0.80 ml/min/kg, and 0.35 +/- 0.15 liters/kg and 2.79 +/- 0.75 ml/min/kg, respectively. There were no significant differences between the kinetic variables in the patients receiving gentamicin or tobramycin. To achieve steady-state peak concentrations between 7 and 9 micrograms/ml and trough concentrations below 2 micrograms/ml, gentamicin patients required 10.3 +/- 3.2 mg/kg/day and tobramycin patients required 11.1 +/- 3.9 mg/kg/day. Because of the large amount of interpatient variability in maintenance dosage requirements, therapy should be initiated with 2.5 mg/kg of gentamicin or tobramycin given every six hours and then individualized on the basis of serum concentrations and clinical response.