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A standard dose of linezolid puts patients with hepatic impairment at risk of overexposure

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Abstract

Purpose

The purpose of this retrospective observational study conducted in patients with hepatic impairment was to assess the variability of linezolid trough concentrations, to determine the risk factors for linezolid overexposure, and to investigate the effect of linezolid overexposure on linezolid-induced thrombocytopenia.

Methods

All enrolled patients received a standard dose (600 mg every 12 h) of linezolid and underwent therapeutic drug monitoring. The Child–Pugh-Turcotte score was used to divide patients into three groups: mild, moderate, and severe hepatic impairment. The risk factors for linezolid overexposure (Cmin > 8 mg/L) and linezolid-induced thrombocytopenia were examined using logistic regression. And the Kaplan–Meier curve was used to describe the association between linezolid overexposure and linezolid-induced thrombocytopenia.

Results

Seventy-seven patients were included, 37 (48.1%) of whom experienced linezolid overexposure. Patients with severe hepatic impairment had a substantially higher median Cmin of linezolid than those with mild (20.7 mg/L vs 5.51 mg/L, P < 0.001) or moderate (20.7 mg/L vs 6.70 mg/L, P = 0.001) hepatic impairment. Severe hepatic impairment was significantly associated with linezolid overexposure (OR 7.037, 95%CI 1.426–34.727, P = 0.017). After linezolid treatment, linezolid-induced thrombocytopenia occurred in 32 (41.6%) patients, and Cmin > 8 mg/L was a significant predictor of linezolid-induced thrombocytopenia (OR 3.024, 95%CI 1.083–8.541, P = 0.035).

Conclusion

Patients with hepatic impairment who received standard doses of linezolid are at greater risk of linezolid overexposure, which may lead to a higher incidence of linezolid-induced thrombocytopenia.

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Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank the authors and all the participants for their time and effort.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82173898), the Programs for Xi’an Science and Technology Bureau (No. 20YXYJ0001(5)), and the Institutional foundation of First Affiliated Hospital of Xi’an Jiaotong University (No. 2019ZYTS-01).

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Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Ru Liao, Yalin Dong, Taotao Wang, Houli Li & Haiyan Dong

  2. Department of International Medical Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Lihong Chen

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  1. Ru Liao
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  2. Yalin Dong
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Contributions

Conceptualization: Haiyan Dong, Yalin Dong, Ru Liao; methodology: Ru Liao, Yalin Dong, Haiyan Dong; formal analysis and investigation: Ru Liao; resources: Lihong Chen, Taotao Wang, Houli Li; writing—original draft: Ru Liao; writing—review and editing: Haiyan Dong; funding acquisition: Haiyan Dong; supervision: Yalin Dong, Haiyan Dong.

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Correspondence to Haiyan Dong.

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The study was approved by the Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University (Xi’an, China) (XJTU1AF2019LSK-163).

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Liao, R., Dong, Y., Chen, L. et al. A standard dose of linezolid puts patients with hepatic impairment at risk of overexposure. Eur J Clin Pharmacol 79, 149–157 (2023). https://doi.org/10.1007/s00228-022-03427-7

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  • DOI: https://doi.org/10.1007/s00228-022-03427-7

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