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Updated: Aug 7, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

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Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of critically ill patients after multiple

Cornelia Buerger1, Nele Plock, Pejman Dehghanyar

  • 1Department of Clinical Pharmacy, Institute of Pharmacy, Freie Universitaet Berlin, D-12169 Berlin, Germany.

Antimicrobial Agents and Chemotherapy
|June 28, 2006
PubMed

Insights

Linezolid effectively distributes into interstitial fluid in critically ill patients, but high variability suggests personalized dosing may be needed for optimal treatment of severe infections.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Linezolid is crucial for treating severe infections, including those caused by methicillin-resistant Staphylococcus strains.
  • Understanding linezolid's penetration into tissue interstitial fluid is vital for optimizing therapy in critically ill patients.

Purpose of the Study:

  • To evaluate linezolid penetration into subcutaneous adipose tissue and skeletal muscle interstitial space fluid (ISF) in patients with sepsis or septic shock.
  • To determine unbound linezolid concentrations in plasma and ISF using microdialysis and pharmacokinetic analysis.

Main Methods:

  • A microdialysis study was conducted with 12 critically ill patients receiving multiple intravenous linezolid infusions.
  • Unbound linezolid concentrations were measured in plasma and ISF via high-performance liquid chromatography.
  • Individual and integrated pharmacokinetic (PK) modeling was performed using WinNonlin.

Main Results:

  • In vivo microdialysis successfully determined steady-state unbound linezolid concentrations in ISF.
  • Linezolid demonstrated good ISF distribution, but with significant interindividual variability.
  • A two-compartment model showed a mean distribution volume of 62.9 L and clearance of 9.18 L/h, with intraindividual changes over time.

Conclusions:

  • Current linezolid dosing may require adjustments for some critically ill patients to maintain effective concentrations in infected tissues.
  • An integrated PK model provides a foundation for developing refined dosing guidelines using a population PK approach.
  • Personalized dosing strategies are essential to ensure effective antimicrobial therapy and avoid subinhibitory concentrations in diverse patient populations.

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