Does the conventional dosage of linezolid necessitate therapeutic drug monitoring?-Experience from a prospective observational study.

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Does the conventional dosage of linezolid necessitate therapeutic drug monitoring?-Experience from a prospective observational study.

Ann Transl Med. 2020 Apr;8(7):493

Authors: Fang J, Chen C, Wu Y, Zhang M, Zhang Y, Shi G, Yao Y, Chen H, Bian X

Abstract
Background: The objectives of the present prospective observational study conducted in patients receiving conventional dosage of linezolid was to define the pharmacodynamic range of linezolid exposure, to assess the inter-individual variability in linezolid concentrations, and to define if therapeutic drug monitoring (TDM) of linezolid may be necessary for Chinese population.
Methods: Patients included in this study underwent linezolid TDM trough concentration (C min) during treatment with a standard regimen in the period between January 2019 and October 2019. Linezolid C min was analyzed with high-performance liquid chromatography (HPLC) method. Logistic regression was used to define the desired range of linezolid C min. Linear regression and univariate logistic regression analysis were carried out to investigate variables associated with inappropriate linezolid plasma exposure.
Results: A total of 84 patients who had 153 linezolid C min assessed were included in the study. Median linezolid C min was 3.43 mg/L (IQR 1.59-5.93). The estimated probability of thrombocytopenia was 50% in the presence of C min of 7.85 mg/L. Approximately 57.52% (88/153) of the samples fell within the desired range of linezolid C min (2-8 mg/L) while 31.37% (48/153) experienced underexposure, and overexposure occurred in 11.11% (17/153) of the patients. No significant linear relationships between either body weight or estimated creatinine clearance (CrCL) and C min were detected. Estimated CrCL ≥100 mL/min was significantly associated with linezolid underexposure (OR 4.121; 95% CI, 1.945-8.731; P<0.001). Estimated CrCL ≤40 mL/min was significantly associated with linezolid overexposure (OR 3.761; 95% CI, 1.324-10.681; P=0.013).
Conclusions: Our results suggest that the pharmacodynamic range of linezolid C min can be defined as 2-8 mg/L for the Chinese population. Renal function partially accounts for the inter-interindividual variability of exposure. The application of TDM might be especially valuable in optimizing linezolid exposure in the majority of patients to avoid therapeutic failure and/or dose-dependent adverse reactions.

PMID: 32395537 [PubMed]