Population pharmacokinetics of unbound ceftriaxone in a critically ill population

To develop a reliable 2-compartment population pharmacokinetic (PK) model for unbound ceftriaxone in a critically ill population and determine an optimal dosing regimen.This was a prospective, single-center, observational study of critically ill patients treated with ceftriaxone. Unbound serum ceftriaxone concentrations were measured using validated ultrafiltration and ultra-performance liquid chromatography-tandem mass spectrometry. PK analysis and dosing simulations were performed using an iterative 2-stage Bayesian fitting procedure and Monte Carlo simulations. The PK/pharmacodynamics (PD) target was attained when unbound serum ceftriaxone concentrations exceeded 4 times the minimum inhibitory concentration (MIC) for ≥ 60% of the dosing interval (ƒT91 patients were enrolled, and 173 unbound ceftriaxone concentrations were acquired. The population PK parameter estimates were hepatic clearance 5.2 ± 0.9 L/h/1.85mWe developed a reliable population PK model for unbound ceftriaxone in a critically ill population. Dosing simulations revealed ƒT