The objective of this study was to develop a population pharmacokinetic model for linezolid in hematooncological patients with sepsis, and to propose dosing optimization based on pharmacokinetic covariates that would lead to improved achievement of the PK/PD target. Therapeutic drug monitoring data from hematooncological patients treated with linezolid for suspected or proven sepsis were analyzed. A pharmacokinetic population model for linezolid was constructed using a nonlinear mixed-effects modeling approach. Monte Carlo simulations were then used to compare various dosing regimens in terms of PK/PD target attainment. A total of 197 linezolid serum concentrations obtained from 22 patients were included in the analysis. Patients' age was found to be the most predictive covariate for linezolid pharmacokinetics. In a patient with a median age of 59 years, the volume of distribution and clearance of linezolid were 46.2 L and 12.1 L/h, respectively. During the first 4 days of therapy, linezolid clearance decreased by 33%. The probability of PK/PD target attainment increased through the individualization of the dose according to the patient's age, administration of a loading dose, and administration of linezolid via continuous infusion. For this scenario, an easy-to-use nomogram was designed.

4th Department of Internal Medicine Hematology University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Department of Anaesthesiology Resuscitation and Intensive Care Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Clinical Biochemistry and Diagnostics University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Institute of Pharmacology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

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