Abstract P-215: PIPERACILLIN PHARMACOKINETICS AND DOSING REGIMEN OPTIMIZATION IN CRITICALLY ILL CHILDREN WITH NORMAL AND AUGMENTED RENAL CLEARANCE

Abstract

Aims & Objectives: Our objectives were to build a pediatric population pharmacokinetic model for Piperacillin, in order to optimize individual dosing regimen. Methods All children admitted in pediatric intensive care unit and receiving intermittent Piperacillin infusions were included. Piperacillin was quantified by high performance liquid chromatography. Pharmacokinetics were described using the non-linear mixed effect modelling software MONOLIX. Monte Carlo simulations were used to optimize dosing regimen, in order to maintain plasma concentration above the minimum inhibitory concentration (16 mg.L-1 for Pseudomonas aeruginosa) throughout the dosing interval (100% fT>MIC). Results We included 50 children with a median (range) post natal age of 27.2 (1.1–222.9) months, median (range) body weight of 11.9 (2.7–50) kg, median (range) PELOD-2 score of 4 (0–16) and median (range) estimated creatinine clearance of 142 (29–675) mL.min-1.m-2. A one compartment model with first-order elimination adequately described the data. Median (range) values for clearance and volume of distribution were respectively 3 (0.71–10) L.h-1 and 3.8 (0.72–25.8) L. Body weight (allometric relationship), estimated creatinine clearance and PELOD-2 severity score were the covariates explaining the estimated between subject variability. To reach the target and according to the simulated dosing regimens, children with acute kidney injury should receive intermittent infusion every 6 hours, administered on 30 minutes. Those with augmented renal clearance should receive a continuous infusion. Conclusions To reach the target, standard intermittent Piperacillin dosing regimen in critically ill children is not appropriate. In addition to body weight, dosing regimens should take into account the creatinine clearance. Continuous infusion is adequate for children with augmented renal clearance.