Clinical pharmacology of tobramycin in children

The pharmacokinetics of tobramycin were evaluated in 50 pediatric patients (two to 18 years of age) with malignancies and normal renal function. Patients receiving either 240 or 300 mg/m2 per 24 hr (8 or 10 mg/kg per 24 hr) divided into doses given every 4 hr had peak serum concentrations (mean +/- standard error) of 3.10 +/- 0.23 microgram/ml and 4.23 +/- 0.25 microgram/ml, respectively, at the end of a 1-hr infusion. Serum concentrations at 4 hr were 0.82 +/- 0.15 and 1.05 +/- 0.15 microgram/ml, respectively. The half-life of the drug was 96.6 min and was inversely correlated with age of the patients. The total clearance rate of tobramycin was 164 +/- 15 mg/min per 1.73 m2 and was directly correlated with age. The mean volume of distribution was 0.42 +/- 0.038 liter/kg and was inversely correlated with age. No accumulation of tobramycin was noted, and no side effects occurred. If therapeutic serum concentrations of tobramycin are to be achieved and maintained in children, the currently recommended dose and frequency of administration should be changed to 300 mg/m2 per 24 hr given in divided doses every 4 hr.