Population pharmacokinetic modeling and simulation-informed ceftazidime dosing in Chinese neonates using quantitative...

Ceftazidime is widely used off-label to treat neonatal infections, underscoring the need for optimized dosing strategies. However, pharmacokinetic (PK) studies in neonates are limited by the challenges of conventional blood sampling. This study applied dried blood spot (DBS) micro-sampling to develop a population PK (PopPK) model to support appropriate ceftazidime dosing regimens in neonates. A prospective PopPK study was conducted in neonates receiving ceftazidime. Blood samples were collected using the Capitainer quantitative DBS (qDBS) device, and concentrations were quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). PopPK modeling was performed in NONMEM. Body weight (WT) and postmenstrual age (PMA) were incorporated a priori using allometric scaling and a sigmoidal maturation function. Additional covariates were evaluated using stepwise selection. Monte Carlo simulations were conducted to assess the probability of target attainment (PTA) for various dosing regimens against the target of 70% fT > MIC. A total of 140 qDBS samples from 72 neonates were analyzed. A one-compartment model adequately described ceftazidime PK. PMA significantly influenced clearance, while WT affected volume of distribution. Simulations indicated that, for neonates with PMA 32-42 weeks, regimens of 25 mg/kg every 6 or 8 h, and 75 mg/kg every 12 h achieved a PTA ≥90% for MIC ≤4 mg/L. A PopPK model for ceftazidime was successfully developed using qDBS samples from neonates. For neonates with PMA 32-42 weeks, dosing regimens of 25 mg/kg every 6 or 8 h and 75 mg/kg every 12 h are recommended to achieve optimal target attainment.