Population pharmacokinetic analysis and dosing regimen optimization of eravacycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii pneumonia

OBJECTIVES: To develop a population pharmacokinetic (PopPK) model of eravacycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia, characterize its pharmacokinetic profile, and optimize dosing regimens to ensure adequate drug exposure in this vulnerable population. METHODS: The plasma concentration of eravacycline was determined using liquid chromatography-tandem mass spectrometry. PopPK analysis was performed using nonlinear mixed-effects modelling, and the optimal dosing regimen was optimized via Monte Carlo simulation. RESULTS: A total of 104 plasma samples were collected from 18 patients for eravacycline concentration determination. The final PopPK model was a two-compartment model with body weight as a significant covariate on peripheral volume of distribution (V2). The population typical values for CL, central volume of distribution (V1) and V2 in the final model were 14.4 L/h, 177.6 L and 383.2 L, respectively. Monte Carlo simulations demonstrated that the PK/PD target for eravacycline was achievable with a standard dose (1 mg/kg, Q12 h) at an MIC of 0.125 mg/L in patients weighing 41-80 kg. However, this fixed-dosing strategy was suboptimal at higher MICs. CONCLUSIONS: This study successfully developed the first PopPK model for eravacycline in critically ill patients with CRAB pneumonia. The findings highlight substantial pharmacokinetic variability and demonstrate that weight-based dosing is crucial to ensure effective exposure, underscoring the necessity of PK/PD-guided personalized therapy.