Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
Linezolid Dosing and Pharmacokinetics in North American Patients With Tuberculosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Maranchick Nicole F, Peloquin Charles A, Haley Connie A
Аннотация
BACKGROUND: Linezolid is recommended in treatment regimens for rifampin- or multidrug-resistant tuberculosis (TB). However, considerable pharmacokinetic variability exists, and long-term use is limited by adverse effects. This study evaluates the pharmacokinetics of linezolid in patients with TB from an international therapeutic drug monitoring (TDM) service.
METHODS: Linezolid trough, 2-hour, and 6-hour postdose clinical samples from across North America were tested by the University of Florida Infectious Disease Pharmacokinetics Laboratory. Total serum concentrations were measured using liquid chromatography-tandem mass spectrometry. TDM was performed, and measurements were compared to typical linezolid concentrations including a trough value of <2 μg/mL and peak value between 12 and 26 μg/mL.
RESULTS: From January 2019 to December 2023, 1604 linezolid samples from 500 patients and 817 unique TDM occasions were analyzed. Trough concentrations were measured on 670 samples (median, 1.19 [range, 0.00-20.06] μg/mL), and 232 troughs (34.6%) were >2 μg/mL. Among trough samples from linezolid dosing of 600 mg daily, 43.2% were >2 μg/mL. Of 600 peak samples, 264 (44%) were outside the typical range, most (89%) being subtherapeutic at <12 μg/mL.
CONCLUSIONS: High serum linezolid trough concentrations were measured in approximately one-third of samples and in >40% of those taking the recommended dose. More than 40% of peak concentrations were outside typical range, of which 89% were <12 μg/mL. This study demonstrates that TDM can be used to identify patients with serum linezolid concentrations outside of targeted ranges, allowing clinicians to make appropriate dose adjustments to improve outcomes.
METHODS: Linezolid trough, 2-hour, and 6-hour postdose clinical samples from across North America were tested by the University of Florida Infectious Disease Pharmacokinetics Laboratory. Total serum concentrations were measured using liquid chromatography-tandem mass spectrometry. TDM was performed, and measurements were compared to typical linezolid concentrations including a trough value of <2 μg/mL and peak value between 12 and 26 μg/mL.
RESULTS: From January 2019 to December 2023, 1604 linezolid samples from 500 patients and 817 unique TDM occasions were analyzed. Trough concentrations were measured on 670 samples (median, 1.19 [range, 0.00-20.06] μg/mL), and 232 troughs (34.6%) were >2 μg/mL. Among trough samples from linezolid dosing of 600 mg daily, 43.2% were >2 μg/mL. Of 600 peak samples, 264 (44%) were outside the typical range, most (89%) being subtherapeutic at <12 μg/mL.
CONCLUSIONS: High serum linezolid trough concentrations were measured in approximately one-third of samples and in >40% of those taking the recommended dose. More than 40% of peak concentrations were outside typical range, of which 89% were <12 μg/mL. This study demonstrates that TDM can be used to identify patients with serum linezolid concentrations outside of targeted ranges, allowing clinicians to make appropriate dose adjustments to improve outcomes.