Disease Condition Affects Amikacin Pharmacokinetics and Dosing in Children

Background:Amikacin treats gram-negative infections. We aimed to concomitantly assess the impact of clinical characteristics and disease condition on amikacin pharmacokinetics (PK) in pediatric burn and oncology patients.Design/Methods:A cohort on amikacin PK in children with burn injuries [1] was pooled with new data of children with cancer. Routine amikacin therapeutic drug monitoring data and clinical characteristics were retrospectively collected. The pooled data were used to develop a two-compartment PK model using non-linear mixed effects modeling. Based on the final model, optimal dosing was simulated, aiming for peak ≥ 64 and trough \u3c 2 mg/L in once daily dosing.Results:Median (5–95th percentiles) age of the 187 patients was 5.8 (0.8–16.3) years. The mean (95%CI) central volume of distribution (V1) was 5.88 (4.82–6.94) L, central clearance (CL) 2.19 (1.86–2.53) L/h, peripheral volume of distribution (V2) 4.93 (2.64–7.22 ) L, and distribution clearance (Q) 0.76 (0.37–1.1.6) L/h. Disease was identified as a significant covariate, and indicated 60% (33-87%) higher CL and 24% (5-43%) higher V1 in burn patients compared to cancer. Age, creatinine clearance and weight were predictors on CL. Covariates on distribution volumes were age (V1, V2) and weight (V1). Burn patients need higher doses than cancer patients to achieve the same targets [figure].Conclusion(s):This first pooled analysis documented that children with burn injuries had higher amikacin CL and V1 compared to those with cancer. Disease condition has to be integrated in pediatric PK model-derived dosing regimens