Helena Barrasa1, Amaia Soraluce2, Elena Usón1, Javier Sainz3, Alejandro Martín1, José Ángel Sánchez-Izquierdo3, Javier Maynar1, Alicia Rodríguez-Gascón2, Arantxazu Isla4. 1. Intensive Care Unit, University Hospital of Alava, C/ Olaguibel 29, Vitoria-Gasteiz, Spain. 2. Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. 3. Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba s/n, Madrid, Spain. 4. 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.
Abstract
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.
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 illpatients. 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 ARCpatients, leading to sub-therapeutic concentrations. Continuous infusion (50 mg/h) provided concentrations ≥2 mg/l in 70% of the ARCpatients. 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.
Authors: Rasha M El-Gaml; Noha M El-Khodary; Rania R Abozahra; Ayman A El-Tayar; Soha M El-Masry Journal: Eur J Clin Pharmacol Date: 2022-05-25 Impact factor: 3.064
Authors: Idoia Bilbao-Meseguer; Helena Barrasa; Alicia Rodríguez-Gascón; Eduardo Asín-Prieto; Javier Maynar; José Ángel Sánchez-Izquierdo; María Ángeles Solinís; Arantxazu Isla Journal: J Intensive Care Date: 2022-04-21
Authors: Ana Alarcia-Lacalle; Helena Barrasa; Javier Maynar; Andrés Canut-Blasco; Carmen Gómez-González; María Ángeles Solinís; Arantxazu Isla; Alicia Rodríguez-Gascón Journal: Pharmaceutics Date: 2021-06-25 Impact factor: 6.321