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JAC Advance Access originally published online on December 24, 2008
Journal of Antimicrobial Chemotherapy 2009 63(3):550-552; doi:10.1093/jac/dkn516
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Pharmacokinetics of linezolid in human non-inflamed vitreous after systemic administration

Juan P. Horcajada1,*, Rebeka Atienza2, María Sarasa3, Dolors Soy4, Alfredo Adán2 and Josep Mensa1

1 Service of Infectious Diseases, Hospital Clínic Universitari, Villaroel 170, 08036 Barcelona, Spain 2 Service of Ophthalmology, Hospital Clínic Universitari, Villaroel 170, 08036 Barcelona, Spain 3 Service of Clinical Pharmacology, Hospital Clínic Universitari, Villaroel 170, 08036 Barcelona, Spain 4 Pharmacy Service, Hospital Clínic Universitari, Villaroel 170, 08036 Barcelona, Spain

Received 28 August 2008; returned 21 October 2008; revised 11 November 2008; accepted 26 November 2008

* Corresponding author. Present address: Service of Internal Medicine and Infectious Diseases, Hospital Universitari del Mar, Passeig Marítim 25-29, 08003 Barcelona, Spain. Tel: +34-9483251; Fax: +34-9483257; E-mail: jhorcajada{at}imas.imim.es

Objectives: To determine the concentration–time curves of linezolid in serum and vitreous from 24 patients undergoing vitrectomy.

Methods: Vitrectomy was performed 1, 2, 4, 8 and 12 h after infusion of 600 mg of linezolid in 20 patients divided into groups of four. Four additional patients were studied 12 h after two separate oral doses of 600 mg of linezolid. Serum samples were obtained 1 h after linezolid administration to determine Cmax; vitreous and a second serum sample were taken simultaneously during the vitrectomy in all patients, and the concentrations of linezolid in vitreous (Cv) and serum (Cs) were determined.

Results: Among patients who received one intravenous dose of 600 mg of linezolid, the highest mean Cv was observed at 4 and 8 h following linezolid administration (3.4 and 3.7 mg/L). The highest mean Cv was observed in patients who received two oral doses of 600 mg of linezolid separated by 12 h (4.5 mg/L), which was higher than the MIC90 for Staphylococcus epidermidis. The highest Cv/Cs ratio was reached 12 h after administration of one and two doses (2.4 and 1.5, respectively).

Conclusions: Microbiologically significant concentrations of linezolid can be achieved in the vitreous of the non-inflamed human eye after intravenous administration of 600 mg, and it is even better after two doses of 600 mg. It appears that linezolid accumulates in the vitreous, achieving potentially useful steady-state concentrations. An evaluation of clinical efficacy is needed to confirm the perceived utility based on the pharmacokinetics.

Keywords: oxazolidinones , eye , penetration


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