Amikacin population pharmacokinetics among paediatric burn patients

IntroductionThe objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.MethodsPopulation-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10-20 mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.ResultsThe analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean Cmax was 33.2 ± 9.4 μg/mL and the mean Cmin was 3.8 ± 4.6 μg/mL. The final covariate model estimated clearance as 5.98 L/h/70 kg (4.97-6.99, 95% CI), the volume of distribution in the central compartment as 16.7 L/70 kg (14.0-19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1 L/70 kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as 3.38 L/h/70 kg (2.44-4.32, 95% CI). In multivariate analyses, current weight (P < 0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.DiscussionChildren with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.