Abstract
Objective Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens.
Methods We performed a retrospective chart review in non-critical pediatric patients (aged 1-12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets.
Results The analysis included 134 amikacin plasma concentrations from 67 patients with a mean +/- standard deviation age of 4.1 +/- 3.9 years and bodyweight of 15 +/- 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 +/- 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 +/- 7.6 and 2.4 +/- 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 1/h and 6.5 1 for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (C-peak)/minimum inhibitory concentration (MIC) >= 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values.
Conclusion The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of >= 8 mg/l.