title: Ocular penetration of linezolid after oral administration in rabbits.
abstract: OBJECTIVE
  The pharmacokinetics of linezolid (LZD) was investigated in rabbit eyes after single and multiple oral administrations.
  
  
  METHODS
  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.
authors.affiliation: Laboratory of Antibiology, Department of Microbiology, University Hospital of Strasbourg, Strasbourg, France. mahers_fr@yahoo.fr
authors.forename: Maher
authors.initials: M
authors.lastname: Saleh
authors.forename: Sophie
authors.initials: S
authors.lastname: Lefevre
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
authors.forename: Gilles
authors.initials: G
authors.lastname: Prevost
authors.forename: David
authors.initials: D
authors.lastname: Gaucher
authors.forename: Claude
authors.initials: C
authors.lastname: Speeg-Schatz
authors.forename: François
authors.initials: F
authors.lastname: Jehl
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D009877:Endophthalmitis / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D000069349:Linezolid; D023303:Oxazolidinones / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D014018:Tissue Distribution; D014822:Vitreous Body / Q000737:chemistry*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid