Amikacin dosing in neonates: evaluation of a dosing chart based on population pharmacokinetic data

Abstract

A dosing chart for amikacin (AMK) was developed from average pharmacokinetic parameters for infants with varying postnatal ages and birth weights ranging from less than 800 to greater than 2,500 g. This chart was then evaluated in 38 infants (648-5,404 g; 25-43 weeks postconceptional age, estimated glomerular filtration rate (GFR) 9.0-49.0 ml/min/1.73 m2) with suspected infection by comparison of predicted versus observed steady-state peak (Cssmax) and trough (Cssmin) serum AMK concentrations. Additionally, the apparent elimination half-life (t1/2) for AMK was determined for each infant using two postinfusion serum concentrations obtained at steady state. As expected, linear correlations were found between the elimination rate constant (Ke) for AMK and both postconceptional age (PCA; y = -0.54 + 0.005x; r = 0.59, p less than 0.01) and estimated GFR (y = 0.05 + 0.002x; r = 0.65; p less than 0.01). The dosing chart produced desired therapeutic Cssmax values (e.g. 20-30 micrograms/ml) in 76.3% of patients, with 2.6 and 21.1% having values less than 20 and greater than 30 micrograms/ml, respectively. Desired therapeutic Cssmin serum AMK concentrations (e.g. 4-10 micrograms/ml) were obtained in 71.1% of patients, with 10.5 and 18.4% having concentrations of less than 4 and greater than 10 micrograms/ml, respectively. However, significant linear correlations were not found between the predicted versus observed values for either Cssmax or Cssmin. The AMK dosing chart for neonates enables attainment of desired therapeutic serum concentrations in the majority of infants at the initiation of therapy despite wide variability in PCA, birth weights and estimated GFR.