Pharmaceutics
Population Pharmacokinetics of Amikacin and Monte Carlo Simulation Study in Critically Ill Septic Patients Undergoing Continuous Renal Replacement Therapy with CytoSorb® or oXiris®
By Nikolina Spiric, Peđja Kovačević, Tijana Kovačević and 8 others.
Abstract
Background
Adsorptive devices, including CytoSorb® and oXiris®, are increasingly added to continuous renal replacement therapy (CRRT) in septic patients, but their effect on amikacin clearance and exposure is unknown. We characterized amikacin pharmacokinetics (PK) during adsorptive CRRT and derived dosing implications.
Methods
A population PK model was developed in 24 critically ill septic patients (using NONMEM ver. 7.5.0), separating intrinsic clearance (CL_int) from filter-specific extracorporeal clearance (CL_CRRT). Sparse pre-filter sampling was handled using informative priors for distribution parameters. Robustness was assessed by sampling-importance-resampling (SIR) and prediction-corrected visual predictive checks (pcVPC). Monte Carlo simulations (9000 subjects) evaluated probability of target attainment (PTA; Cmax/MIC ≥ 8, AUC24/MIC ≥ 75) and cumulative fraction of response (CFR) against four Gram-negative pathogens across three regimens (500 mg q8h, 500 mg q24h, 1500 mg q24h), two filters, and three connection times.