Dataset Information

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

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.

SUBMITTER: Fang J

PROVIDER: S-EPMC7210126 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Fang Jie J Chen Congqin C Wu Yan Y Zhang Min M Zhang Ying Y Shi Guochao G Yao Yijin Y Chen Hong H Bian Xiaolan X

Annals of translational medicine 20200401 7

<h4>Background</h4>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.<h4>Methods</h4>Patients included in this study underwent linezolid TDM trough concentration (<i>C</i> <sub>min</su ...[more]

PMID: 32395537

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Project description:To avoid the failures in therapy with psychotropic drugs, treatments can be personalized by applying the results of therapeutic drug monitoring and pharmacogenetic testing. The objective of the present single-center observational study was to describe the changes in psychotropic drug management prompted by therapeutic drug monitoring and pharmacogenetic testing, and to compare the effective drug concentration based on metabolic status with the dose predicted using an in silico decision tool for drug-drug interactions. The study was conducted in psychiatry wards at Lille University Hospital (Lille, France) between 2016 and 2020. Patients with data for at least one therapeutic drug monitoring session or pharmacogenetic test were included. Blood tests were performed for 490 inpatients (mainly indicated by treatment monitoring or failure) and mainly concerned clozapine (21.4%) and quetiapine (13.7%). Of the 617 initial therapeutic drug monitoring tests, 245 (40%) complied with good sampling practice. Of the patients, 51% had a drug concentration within the therapeutic range. Regardless of the drug concentration, the drug management did not change in 83% of cases. Thirty patients underwent pharmacogenetic testing (twenty-seven had also undergone therapeutic drug monitoring) for treatment failure; the plasma drug concentration was outside the reference range in 93% of cases. The patient's metabolic status explained the treatment failure in 12 cases (40%), and prompted a switch to a drug metabolized by another CYP450 pathway in 5 cases (42%). Of the six tests that could be analyzed with the in silico decision tool, all of the drug concentrations after adjustment were included in the range estimated by the tool. Knowledge of a patient's drug concentration and metabolic status (for CYD2D6 and CYP2C19) can help clinicians to optimize psychotropic drug adjustment. Drug management can be optimized with good sampling practice, support from a multidisciplinary team (a physician, a geneticist, and clinical pharmacist), and decision support tools.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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