Ocular penetration of linezolid after oral administration in rabbits

The pharmacokinetics of linezolid (LZD) was investigated in rabbit eyes after single and multiple oral administrations.

Pharmacology Laboratory, University Hospital of Strasbourg, Strasbourg, France.

Twelve New Zealand rabbits were divided into 2 groups: an oral dose of 120 mg (35 mg/kg) was administrated in group 1 (n=6), and a multiple-dose protocol targeting the steady state (120 mg twice a day for 3 days) was given in group 2 (n=6). Serum (s) and vitreous (v) samples were collected after 0, 30, and 45 min and after 1, 2, 4, 6, 8, and 12 h. LZD concentrations were measured by high-performance liquid chromatography.

LZD exhibited a mean C(max) in serum of 13.9±4.5 (standard deviation) mg/L after a T(max) of 1 h in group 1 and 18.0±6.5 mg/L after a T(max) of 30 min in group 2. The vitreal peak occurred at 2 h in both groups with an intraocular C(max) of 3.0±1.3 mg/L in group 1 and 4.5±1.4 mg/L in group 2. The resulting area under the concentration-time curve in vitreous at the steady state compared with the area under the concentration-time curve calculated after a single dose increased significantly (28.7±7.7 vs. 18.3±2.1 mg·h/L, respectively, p<0.05). The time that serum concentration exceeded the minimum inhibitory concentrations (T>MIC) in group 2 was eventually >40% for MIC up to 3 mg/L in rabbit vitreous.

Although a single oral dose produced intraocular concentrations barely sufficient to induce bacterial eradication, a multiple-dose regimen provided intraocular levels exceeding the MICs of most Gram-positive organisms responsible for endophthalmitis.