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Pharmacological Issues of Linezolid

An Updated Critical Review

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Abstract

Linezolid is the first oxazolidinone agent introduced into clinical practice for use against Gram-positive bacteria that are resistant to β-lactams and glycopeptides, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). An optimal antibacterial effect is achieved when plasma drug concentrations are above the minimum inhibitory concentration (MIC) [T>MIC] for the entire length of treatment and the ratio between the area under the plasma concentrationtime curve (AUC) and the MIC (AUC/MIC) is greater than 100, as is most commonly obtained with administrationof the standard dosage of linezolid 600 mg twice daily. A wide tissue distribution, including the CNS and respiratory tract, nearly linear pharmacokinetics and good tolerability are additional characteristics of linezolid. However, variability in the drug pharmacokinetics associated with clinical conditions (e.g. sepsis, burn injuries, end-stage renal disease, cystic fibrosis), haemodialysis and/or young age may lower the T>MIC and the AUC/MIC ratio, thus impairing both antibacterial activity and prevention of mutants. In most cases, changes in the dosage or in the schedule of administration (e.g. an additional [third] daily dose) may improve the effectiveness of linezolid. It is worth noting that linezolid could affect its own metabolism as a result of protein synthesis inhibition in mitochondria, and this could lead to high plasma concentrations and an increased risk of non-negligible toxicities. The latter may be reported during long-term administration of linezolid or in the presence of some pathological conditions (e.g. renal disease or kidney transplantation) associated with high plasma drug concentrations. Therefore, treatment optimization should be considered a requirement for more effective and tolerable use of the drug, particularly in special populations.

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Division of Pharmacology and Chemotherapy, Department of Internal Medicine, Via Roma 55, 56126, Pisa, Italy

    Antonello Di Paolo, Emanuele Guidotti, Romano Danesi & Mario Del Tacca

  2. Intensive Care Unit, Santa Chiara University Hospital, Pisa, Italy

    Paolo Malacarne

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Di Paolo, A., Malacarne, P., Guidotti, E. et al. Pharmacological Issues of Linezolid. Clin Pharmacokinet 49, 439–447 (2010). https://doi.org/10.2165/11319960-000000000-00000

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