Ocular penetration of topically applied linezolid in a rabbit model.
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.
Saleh
Maher
M
Department of Microbiology, Laboratory of Antibiology, University Hospital of Strasbourg, 1 Place de l'Hopital, 67000 Strasbourg, France. maher.saleh@chru-strasbourg.fr
Jehl
François
F
Dory
Anne
A
Lefevre
Sophie
S
Prevost
Gilles
G
Gaucher
David
D
Sauer
Arnaud
A
Speeg-Schatz
Claude
C
Bourcier
Tristan
T
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
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid