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Aqueous and vitreous penetration of linezolid and levofloxacin after oral administration.

Author(s): George JM, Fiscella R, Blair M, Rodvold K, Ulanski L, Stokes J, Blair N, Pontiggia L

Affiliation(s): Department of Pharmacy Practice, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA. j.george@usp.edu

Publication date & source: 2010-12, J Ocul Pharmacol Ther., 26(6):579-86. Epub 2010 Oct 26.

Publication type: Randomized Controlled Trial

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. METHODS: 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 (mug/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 (mug/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.

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