Multiple-dose amikacin kinetics in pediatric oncology patients

Amikacin kinetics was studied in 8 pediatric oncology patients who received the drug by intravenous infusion over 30 or 60 min at a dose of 5 mg/kg every 6 or 8 hr. This regimen is recommended but, due to patient variability, patients should be monitored. Dosing intervals during 1 or 2 and 3 or 4 days of therapy were studied with serum samples collected before and at the end of the infusion and serially to the end of the dosing interval. The data appeared consistent with and were analyzed according to 1-compartment model. An equation describing serum concentration with time for the multiple-dose case was fit to each patient's multiple-interval data with nonlinear regression. Half-life averaged 1.2 hr. volume of distribution 0.24 l/kg, and total body clearance 109 ml/min/1.73 m2 or 2.51 ml/min/kg. The volume of distribution and the clearance are greater than reported for adults and probably account for the larger dose needed to achieve and maintain therapeutic levels. Although the total daily dose was greater than previously reported, there were no signs of toxicity, although therapuetic concentrations were maintained.