A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital-wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

作者：Pea Federico^*; Cojutti Pier Giorgio; Baraldo Massimo

来源：Basic and Clinical Pharmacology and Toxicology, 2017, 121(4): 303-308.

DOI：10.1111/bcpt.12797

A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (C-min) during treatment with conventional doses of 600mg every 12hr in the period between January 2007 and June 2016. The desired range of C-min was set between 2 and 7mg/L (underexposure, C-min<2mg/L; overexposure, C-min>7mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid C-min. One thousand and forty-nine patients had 2484 linezolid C-min assessed during treatment with conventional doses. Median (IQR) linezolid C-min was 5.08mg/L (2.78-8.52mg/L). Linezolid C-min was within the desired range in 50.8% of cases (1262/2484). Overexposure (n=821; 33%) occurred much more frequently than underexposure (n=401; 16.2%) and was severe (>20mg/L) in 3.9% of cases (98/2484). Linezolid overexposure was significantly associated with CrCLC-G estimates 40mL/min. (OR 1.463; 95% CI 1.124-1.904, p=0.005). Linezolid underexposure was significantly associated with CrCLC-G estimates >100mL/min. (OR 3.046; 95% CI 2.234-4.152, p<0.001). Linezolid C-min was not correlated linearly with CrCLC-G (R-2=0.061). Variability in renal function explained only partially the very wide interindividual linezolid C-min variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients.

• 出版日期2017-10