PMID- 32112965
OWN - NLM
STAT- MEDLINE
DCOM- 20200724
LR  - 20200724
IS  - 1878-3511 (Electronic)
IS  - 1201-9712 (Linking)
VI  - 93
DP  - 2020 Apr
TI  - Impact of augmented renal clearance on the pharmacokinetics of linezolid: 
      Advantages of continuous infusion from a pharmacokinetic/pharmacodynamic 
      perspective.
PG  - 329-338
LID - S1201-9712(20)30102-8 [pii]
LID - 10.1016/j.ijid.2020.02.044 [doi]
AB  - 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.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Barrasa, Helena
AU  - Barrasa H
AD  - Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, 
      Vitoria-Gasteiz, Spain.
FAU - Soraluce, Amaia
AU  - Soraluce A
AD  - Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, 
      Centro de Investigacion Lascaray-ikergunea, University of the Basque Country 
      UPV/EHU, Vitoria-Gasteiz, Spain.
FAU - Uson, Elena
AU  - Uson E
AD  - Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, 
      Vitoria-Gasteiz, Spain.
FAU - Sainz, Javier
AU  - Sainz J
AD  - Intensive Care Unit, Doce de Octubre Hospital, Avda de Cordoba s/n, Madrid, 
      Spain.
FAU - Martin, Alejandro
AU  - Martin A
AD  - Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, 
      Vitoria-Gasteiz, Spain.
FAU - Sanchez-Izquierdo, Jose Angel
AU  - Sanchez-Izquierdo JA
AD  - Intensive Care Unit, Doce de Octubre Hospital, Avda de Cordoba s/n, Madrid, 
      Spain.
FAU - Maynar, Javier
AU  - Maynar J
AD  - Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, 
      Vitoria-Gasteiz, Spain.
FAU - Rodriguez-Gascon, Alicia
AU  - Rodriguez-Gascon A
AD  - Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, 
      Centro de Investigacion Lascaray-ikergunea, University of the Basque Country 
      UPV/EHU, Vitoria-Gasteiz, Spain.
FAU - Isla, Arantxazu
AU  - Isla A
AD  - Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, 
      Centro de Investigacion Lascaray-ikergunea, University of the Basque Country 
      UPV/EHU, Vitoria-Gasteiz, Spain. Electronic address: arantxa.isla@ehu.eus.
LA  - eng
PT  - Journal Article
DEP - 20200226
PL  - Canada
TA  - Int J Infect Dis
JT  - International journal of infectious diseases : IJID : official publication of the 
      International Society for Infectious Diseases
JID - 9610933
RN  - 0 (Anti-Bacterial Agents)
RN  - ISQ9I6J12J (Linezolid)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacokinetics/therapeutic use
MH  - *Critical Illness/therapy
MH  - Female
MH  - Humans
MH  - Kidney/*metabolism
MH  - Kidney Function Tests
MH  - Linezolid/administration & dosage/*pharmacokinetics/therapeutic use
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Monte Carlo Method
OTO - NOTNLM
OT  - Augmented renal clearance
OT  - Continuous infusion
OT  - Critically ill patients
OT  - Linezolid
OT  - Pharmacokinetic/pharmacodynamics
EDAT- 2020/03/01 06:00
MHDA- 2020/07/25 06:00
CRDT- 2020/03/01 06:00
PHST- 2019/12/09 00:00 [received]
PHST- 2020/02/18 00:00 [revised]
PHST- 2020/02/21 00:00 [accepted]
PHST- 2020/03/01 06:00 [pubmed]
PHST- 2020/07/25 06:00 [medline]
PHST- 2020/03/01 06:00 [entrez]
AID - S1201-9712(20)30102-8 [pii]
AID - 10.1016/j.ijid.2020.02.044 [doi]
PST - ppublish
SO  - Int J Infect Dis. 2020 Apr;93:329-338. doi: 10.1016/j.ijid.2020.02.044. Epub 2020 
      Feb 26.