title: Toxicity comparison of intraocular azithromycin with and without a bioadhesive delivery system in rabbit eyes.
abstract: OBJECTIVE
  To determine whether the addition of a bioadhesive drug-delivery system to topical azithromycin induces intraocular inflammation and damage when introduced intraocularly by different approaches and in varying doses.
  
  
  METHODS
  John A. Moran Eye Center, Salt Lake City, Utah, USA.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Commercial topical azithromycin 1.0% was duplicated, including the benzalkonium chloride, but without inclusion of the Durasite bioadhesive drug-delivery system. Injections of 50 μL, 25 μL, and 10 μL of the antibiotic solutions were administered in a masked fashion to 2 rabbits; 1 eye (study eye) in each rabbit was randomized to receive azithromycin with the delivery system and the fellow eye (control eye) to receive azithromycin without the delivery system. Two rabbits had topical drops of each solution placed after a 2.8 mm incision was created. Masked slitlamp examinations, pachymetry, and intraocular pressure (IOP) were determined 1 day and 2 days postoperatively. The animals were humanely killed, and the endothelial density and histopathology were examined.
  
  
  RESULTS
  The IOP (P<.001), pachymetry (P<.001), and signs of inflammation (P=.38 to .003) were consistently higher in the study eye, especially at the 50 μL dose, than in the control eye. This was confirmed by histopathology.
  
  
  CONCLUSIONS
  If the drug-delivery system gains access to the anterior chamber, it may cause substantial corneal edema and inflammation, even at low doses and after topical administration.
authors.affiliation: University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Goecks
authors.forename: Liliana
authors.initials: L
authors.lastname: Werner
authors.forename: Nick
authors.initials: N
authors.lastname: Mamalis
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Fuller
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
authors.forename: Shaheen C
authors.initials: SC
authors.lastname: Kavoussi
authors.forename: Mark
authors.initials: M
authors.lastname: Hill
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olson
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017963:Azithromycin / Q000633:toxicity*; D002452:Cell Count; D015715:Corneal Edema / Q000139:chemically induced* / Q000473:pathology; D055954:Corneal Endothelial Cell Loss / Q000139:chemically induced* / Q000473:pathology; D016503:Drug Delivery Systems; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000473:pathology; D007429:Intraocular Pressure / Q000187:drug effects; D007634:Keratitis / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009883:Ophthalmic Solutions / Q000633:toxicity; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D017963:Azithromycin