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The effects of drug-drug interaction on linezolid pharmacokinetics: A systematic review

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Abstract

Objectives

Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid.

Methods

In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: “Linezolid” and “interaction,” or “interact,” or “drug-drug interaction,” or “co-treatment,” or “cotreatment,” or “combined,” or “combination.”

Results

A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58–0.77) and 0.63 (95%CI 0.43–0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49–2.13).

Conclusions

This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.

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Data availability

All the data used for this publication is presented in the main article.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Qiang Xu, Yanlei Sang, Anna Gao & Lu Li

  2. Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Clinical Evaluation and Translational Research, Hangzhou, China

    Qiang Xu & Lu Li

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Contributions

Qiang Xu and Lu Li designed the study. Qiang Xu, Yanlei Sang, and Anna Gao investigated the reviews and data. Qiang Xu wrote the original draft; Lu Li reviewed and edited the manuscript. All authors agreed to submit the final version to the journal and agreed to be accountable for all aspects of the work.

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Correspondence to Lu Li.

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This systematic review was registered in PROSPERO (CRD42023453429) on 21/08/2023.

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Xu, Q., Sang, Y., Gao, A. et al. The effects of drug-drug interaction on linezolid pharmacokinetics: A systematic review. Eur J Clin Pharmacol (2024). https://doi.org/10.1007/s00228-024-03652-2

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