Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis
- 1 November 2010
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 54 (11), 4605-4610
- https://doi.org/10.1128/aac.00177-10
Abstract
The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [ C min ] and peak [ C max ] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC 24 ]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously ( n = 58) or orally ( n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min , 14.70 mg/liter [10.57 to 19.64] for C max , and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC 24 ). Linezolid C min was linearly correlated with estimated AUC 24 ( r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC 24 /MIC 90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC 24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.This publication has 37 references indexed in Scilit:
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