title: Ocular penetration of topically applied linezolid in a rabbit model.
abstract: OBJECTIVE
  To evaluate ocular penetration of topically applied linezolid, a new antibiotic agent targeted against gram-positive organisms.
  
  
  METHODS
  Laboratory of Pharmacology, University Hospital of Strasbourg, Strasbourg, France.
  
  
  METHODS
  New Zealand White rabbits were divided into 3 equal groups. One drop of 50 microL (2 mg/mL) linezolid was administrated in Group 1. In Group 2, eyes were dosed in accordance with a keratitis protocol (1 drop of 2 mg/mL every 15 minutes for 1 hour). Aqueous humor was sampled 6 times from immediately after to 3 hours after drop delivery. In Group 3, a keratitis protocol was implemented before the animals were humanely killed. Conjunctiva, cornea, vitreous, and blood samples were collected 1 hour and 2 hours after the last drop. Linezolid concentrations were measured by high-performance liquid chromatography.
  
  
  RESULTS
  Each group comprised 8 rabbits. In Group 1 and Group 2, the peak linezolid concentration in the aqueous humor (mean 0.87 mg/L +/- 0.16 [SD] and 2.17 +/- 0.4 mg/L, respectively) was 45 minutes after the last drop delivery. In Group 3, the concentrations 1 hour and 2 hours after the last drop were higher than 3 microg/g in the conjunctiva samples and higher than 4 microg/g in the cornea samples. The linezolid concentration in the vitreous and serum was negligible.
  
  
  CONCLUSIONS
  Linezolid levels in the aqueous humor, conjunctiva, and cornea exceeded the minimum inhibitory concentration of most gram-positive organisms that cause bacterial keratitis and endophthalmitis. Linezolid could be a valuable alternative in cases of increased resistance to vancomycin.
authors.affiliation: Department of Microbiology, Laboratory of Antibiology, University Hospital of Strasbourg, 1 Place de l'Hopital, 67000 Strasbourg, France. maher.saleh@chru-strasbourg.fr
authors.forename: Maher
authors.initials: M
authors.lastname: Saleh
authors.forename: François
authors.initials: F
authors.lastname: Jehl
authors.forename: Anne
authors.initials: A
authors.lastname: Dory
authors.forename: Sophie
authors.initials: S
authors.lastname: Lefevre
authors.forename: Gilles
authors.initials: G
authors.lastname: Prevost
authors.forename: David
authors.initials: D
authors.lastname: Gaucher
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sauer
authors.forename: Claude
authors.initials: C
authors.lastname: Speeg-Schatz
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D000069349:Linezolid; D023421:Models, Animal; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid