Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation
Amaia Soraluce,
Helena Barrasa,
Eduardo Asín-Prieto,
Jose Ángel Sánchez-Izquierdo,
Javier Maynar,
Arantxazu Isla,
Alicia Rodríguez-Gascón
Affiliations
Amaia Soraluce
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain
Helena Barrasa
Intensive Care Unit, Araba University Hospital, 01004 Vitoria-Gasteiz, Spain
Eduardo Asín-Prieto
Pharmacometrics & Systems Pharmacology Research Unit, Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
Jose Ángel Sánchez-Izquierdo
Intensive Care Unit. Doce de Octubre University Hospital, 28041 Madrid, Spain
Javier Maynar
Intensive Care Unit, Araba University Hospital, 01004 Vitoria-Gasteiz, Spain
Arantxazu Isla
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain
Alicia Rodríguez-Gascón
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain
Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.
