title: Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations.
abstract: BACKGROUND
  Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti-inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses.
  
  
  OBJECTIVE
  To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria.
  
  
  METHODS
  Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty-three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined.
  
  
  RESULTS
  At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half-life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier-disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC(50) and MIC(90) for many gram-positive equine pathogens.
  
  
  CONCLUSIONS
  This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC ≤ 0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Schnabel
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
authors.forename: T J
authors.initials: TJ
authors.lastname: Divers
authors.forename: C
authors.initials: C
authors.lastname: Altier
authors.forename: M S
authors.initials: MS
authors.lastname: Aprea
authors.forename: T M
authors.initials: TM
authors.lastname: McCarrel
authors.forename: L A
authors.initials: LA
authors.lastname: Fortier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000737:chemistry; D019540:Area Under Curve; D001419:Bacteria / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood* / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010865:Pilot Projects; D013582:Synovial Fluid / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline