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

摘要

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.