Ocular Penetration of Linezolid After Oral Administration in Rabbits

Abstract

Abstract

Purpose:

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

Setting:

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

Methods:

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.

Results:

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.

Conclusions:

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.