Abstract P-216: POPULATION PHARMACOKINETIC MODEL TO OPTIMIZE DOSING REGIMEN IN CRITICALLY ILL CHILDREN

Abstract

Aims & Objectives: The aim of this study was to build a population pharmacokinetic model for cefotaxime in order to optimize individual dosing regimens for critically ill children. Methods All children and receiving intermittent cefotaxime infusions were included. Cefotaxime was quantified by high-performance liquid chromatography. Pharmacokinetics were described using the non-linear mixed-effect modeling software MONOLIX, and Monte Carlo simulations were used to optimize dosing regimen in order to maintain serum concentrations above the target concentration (defined at 2 mg·L−1) throughout the dosing interval. Results We included 49 children with a median (range) postnatal age of 23.7 (0.2–229) months, and median body weight (range) of 10.9 (2.5–68) kg. A one-compartment model with first-order elimination adequately described the data. Median (range) values for cefotaxime clearance and volume of distribution were 0.97 (0.3–7.1) L·h−1 and 0.3 (0.2–0.41) L·kg−1, respectively. Body weight and postnatal age were statistically significant covariates. Cefotaxime-calculated residual concentrations were low, and no patient succeeded in attaining the target. Unlike intermittent administration, a dosing regimen of 100 mg·kg−1·day−1 administered by continuous infusion provided a probability of target attainment of 100%, regardless of age and weight. Conclusions Standard intermittent cefotaxime dosing regimens in critically ill children are not adequate to reach the target. We showed that, for the same daily dose, continuous infusion was the only administration that enabled the target to be attained, for children over 1 month of age. As continuous administration is achievable in the pediatric intensive care unit, it should be considered for clinical practice.