title: Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs.
abstract: BACKGROUND
  The purpose of the present study was to examine the potential ocular and systemic toxicity and toxicokinetics/pharmacokinetics of sustained-release dexamethasone in canines.
  
  
  METHODS
  In this non-randomized study, intracanalicular depots (dexamethasone-loaded or placebo vehicle) were inserted into both eyes of 33 beagles. Tear fluid and plasma were collected for toxicokinetic/pharmacokinetic analysis of dexamethasone, ophthalmic examinations were performed for signs of toxicity, and urine and blood samples were collected for urinalysis, hematology, clinical chemistry, and coagulation analysis. Animals were observed daily for signs of toxicity. Macroscopic and microscopic evaluations were performed.
  
  
  RESULTS
  Mean dexamethasone tear fluid concentration from the dexamethasone group decreased from 4245 ng/mL 6-h post-insertion to 1044 ng/mL on Day 35. All plasma dexamethasone levels were below the limit of quantitation. No systemic or ocular toxicities were attributed to the dexamethasone depot.
  
  
  CONCLUSIONS
  Sustained-release dexamethasone produced no identifiable ocular or systemic toxicity in this animal model, and pharmacokinetics demonstrated a tapered, sustained drug release.
  
  
  BACKGROUND
  Ocular Therapeutix.
authors.affiliation: Ocular Therapeutix, 34 Crosby Drive, Bedford, MA, USA. adriscoll@ocutx.com.
authors.forename: Arthur
authors.initials: A
authors.lastname: Driscoll
authors.affiliation: Ocular Therapeutix, 34 Crosby Drive, Bedford, MA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Blizzard
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004285:Dogs; D005123:Eye; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male
chemical_list: D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D003907:Dexamethasone
keywords: Canines; Dexamethasone; Drug concentration; Drug delivery; Intracanalicular depot; Pharmacokinetics; Punctum plug; Sustained release; Toxicity; Toxicokinetics