Population pharmacokinetics of caspofungin in critically ill Chinese children: a prospective observational study

While caspofungin is increasingly used to treat invasive fungal infections in pediatric intensive care unit (PICU) patients, its pharmacokinetic profile in this population remains poorly understood, and current dosing regimens are not firmly supported by scientific evidence. This study aimed to characterize the population pharmacokinetics of caspofungin in critically ill children and to identify dosing strategies for optimal exposure. The prospective clinical study was conducted among pediatrics in PICU. Population pharmacokinetic analysis and Monte Carlo simulations were performed. A total of 138 plasma samples collected from 29 pediatric patients (0.33-16 years) were included in the final analysis. The two-compartment model with allometric scaling on body surface area (BSA, exponential 1 for volume of distribution and 0.66 for clearance) accurately described time courses of caspofungin. Extracorporeal membrane oxygenation (ECMO) significantly increased the central volume of distribution (effect coefficient 18.2). There was no significant difference in area under the concentration curve (AUC) between patients with and without ECMO support. Simulations demonstrated that tAUC_ss,24h/MIC-based PTA results showed no significant differences between ECMO and non-ECMO groups and supported the current dosing regimen. A fixed maintenance dose (MD) is appropriate for patients with BSA ≥ 1.4 m², while the standard BSA-based MD remains preferable for those with BSA <1.4 m². Our study confirmed the recommended caspofungin dosing regimen in Chinese critically ill PICU patients. Although the number of patients receiving ECMO in this study was limited, future studies with a larger ECMO population are warranted to further validate these findings.This study is registered with ClinicalTrials.gov as NCT04961593.