Impact of augmented renal clearance on the pharmacokinetics of linezolid: Advantages of continuous infusion from a pharmacokinetic/pharmacodynamic perspective.

Autor:	Barrasa H; Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, Vitoria-Gasteiz, Spain., Soraluce A; Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain., Usón E; Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, Vitoria-Gasteiz, Spain., Sainz J; Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba s/n, Madrid, Spain., Martín A; Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, Vitoria-Gasteiz, Spain., Sánchez-Izquierdo JÁ; Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba s/n, Madrid, Spain., Maynar J; Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, Vitoria-Gasteiz, Spain., Rodríguez-Gascón A; Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain., Isla A; Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. Electronic address: arantxa.isla@ehu.eus.
Jazyk:	angličtina
Zdroj:	International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases [Int J Infect Dis] 2020 Apr; Vol. 93, pp. 329-338. Date of Electronic Publication: 2020 Feb 26.
DOI:	10.1016/j.ijid.2020.02.044
Abstrakt:	Objectives: The aim of this study was to assess the influence of renal function, in particular the presence of augmented renal clearance (ARC), on the pharmacokinetics of linezolid in critically ill patients. The effect of continuous infusion on the probability of therapeutic success from a pharmacokinetic/pharmacodynamic (PK/PD) perspective was also evaluated. Methods: Seventeen patients received linezolid (600 mg every 12 h) as a 30-min infusion and 26 as a continuous infusion (50 mg/h). The PK parameters were calculated and the probability of PK/PD target attainment (PTA) was estimated by Monte Carlo simulation (MCS) for different doses administered by intermittent (600 mg every 12 h or 600 mg every 8 h) or continuous infusion (50 mg/h or 75 mg/h). Results: In patients without ARC, the standard dose was adequate to attain the PK/PD target. However, linezolid clearance was significantly higher in ARC patients, leading to sub-therapeutic concentrations. Continuous infusion (50 mg/h) provided concentrations ≥2 mg/l in 70% of the ARC patients. MCS revealed that concentrations ≥2 mg/l would be reached in >90% of patients receiving 75 mg/h. Conclusions: ARC increases linezolid clearance and leads to a high risk of underexposure with the standard dose. Continuous infusion increases the PTA, but an infusion rate of 75 mg/h should be considered to ensure concentrations ≥2 mg/ml. (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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