Population pharmacokinetics and dose optimization of ceftazidime in critically ill children

Abstract

ObjectiveThe aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.MethodsWe performed a prospective pharmacokinetic study on critically ill children aged 0.03–15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% fT > minimum inhibitory concentration (MIC).ResultsThis study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) >90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets in vivo with the commonly used dose of ceftazidime.ConclusionThe population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.Clinical Trial Registrationhttps://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.