title: Does orally administered doxycycline reach the tear film?
abstract: OBJECTIVE
  Orally administered doxycycline, a broad-spectrum antibiotic, is an established treatment for ocular surface diseases, particularly rosacea, meibomian gland dysfunction and recurrent epithelial cell erosion. In recent times, its efficacy in treating these diseases has been ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and both MMP and interleukin-1 (IL-1) synthesis. Since these functions are concentration-dependent, the aim of this project was to determine whether sufficient doxycycline reached the tear film to fulfil these roles in vivo.
  
  
  METHODS
  Doxycycline was extracted with 1-butanol from tear and blood plasma samples obtained from patients with ocular surface disease and healthy individuals and quantified spectrophotometrically. The MMPs present in the patients tear films before and during doxycycline treatment were analysed zymographically.
  
  
  RESULTS
  The quantity of doxycycline detected in the blood plasma samples of patients undergoing treatment ranged from 1.83 to 13.18 microM. Although doxycycline was not detected in their tear samples, the treatment caused the disappearance of the MMPs symptomatic of disease progression.
  
  
  CONCLUSIONS
  The inability to detect doxycycline in the tear film of patients undergoing treatment indicates that doxycycline does not directly inhibit MMP activity or the synthesis/secretion of these proteases and IL-1 from corneal epithelial cells.
authors.affiliation: University of Bristol, Academic Unit of Ophthalmology, Lower Maudlin Street, Bristol BS1 2LX, UK. val.smith@bristol.ac.uk
authors.forename: V A
authors.initials: VA
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Khan-Lim
authors.forename: L
authors.initials: L
authors.lastname: Anderson
authors.forename: S D
authors.initials: SD
authors.lastname: Cook
authors.forename: A D
authors.initials: AD
authors.lastname: Dick
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D018450:Disease Progression; D004318:Doxycycline / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005141:Eyelid Diseases / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis; D008537:Meibomian Glands / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012393:Rosacea / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013666:Tears / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D007375:Interleukin-1; D020782:Matrix Metalloproteinases; D004318:Doxycycline