Aqueous and vitreous penetration of linezolid and levofloxacin after oral administration

J Ocul Pharmacol Ther. 2010 Dec;26(6):579-86. doi: 10.1089/jop.2010.0022. Epub 2010 Oct 26.

Abstract

Purpose: To evaluate the time course of drug concentrations achieved in aqueous (AQ), vitreous (V), and serum (S) compartments after oral administration of linezolid and levofloxacin.

Design: Randomized, clinical trial.

Settings: Clinical practice.

Patient population: Sixteen patients (16 eyes) undergoing vitrectomy who had not had a prior pars plana vitrectomy in the study eye were randomly assigned to one of 4 groups.

Intervention: AQ, V, and S samples were obtained from all subjects after single concomitant doses of linezolid 600 mg and levofloxacin 750 mg between 1 and 12 h before the procedure: group A = 1-3 h; group B = 3-6 h; group C = 6-9 h; group D = 9-12 h.

Main outcome measures: AQ, V, and S concentrations of linezolid and levofloxacin.

Results: Overall mean concentrations ± standard deviation (μg/mL) achieved by linezolid in AQ, V, and S compartments were 3.32 ± 2.06, 2.98 ± 1.87, and 7.91 ± 3.94, respectively. Overall mean concentrations ±standard deviation (μg/mL) achieved by levofloxacin in AQ, V, and S compartments were 2.19 ± 1.92, 1.95 ± 1.27, and 7.38 ± 3.47, respectively.

Conclusions: Single concomitant doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentration for 90% of common ocular gram-positive and gram-negative pathogens up to 12 h after administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of endophthalmitis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / pharmacokinetics*
  • Acetamides / pharmacology
  • Administration, Oral
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Aqueous Humor / metabolism
  • Drug Therapy, Combination
  • Endophthalmitis / prevention & control
  • Female
  • Humans
  • Levofloxacin*
  • Linezolid
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Ofloxacin / administration & dosage
  • Ofloxacin / pharmacokinetics*
  • Ofloxacin / pharmacology
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / pharmacokinetics*
  • Oxazolidinones / pharmacology
  • Time Factors
  • Tissue Distribution
  • Vitrectomy / methods
  • Vitreous Body / metabolism

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Levofloxacin
  • Ofloxacin
  • Linezolid