title: Pharmacokinetics and efficacy of Bioerodible Dexamethasone implant in Concanavalin A-induced uveitic cataract rabbit model.
abstract: OBJECTIVE
  To advance therapy for the treatment of concurrent uveitis and post-cataract surgical inflammation; we evaluated pharmacokinetics and pharmacodynamics of Bioerodible Dexamethasone Implant (BDI) containing 0.3 mg of dexamethasone (DXM) in Concanavalin A (Con A) induced uveitis followed by phacoemulsification in New Zealand White (NZW) rabbits.
  
  
  METHODS
  The BDI was implanted in the inferior fornix of the capsular bag after intravitreal injection of Con A and ensuing phacoemulsification in NZW rabbits; standard-of-care topical 0.1% dexamethasone drops served as control. DXM was quantified by liquid chromatography-tandem mass spectrometry and pharmacokinetics of DXM in disease vs. healthy eyes was compared. All eyes were assessed clinically using slit lamp biomicroscopy and Draize scoring scale. Retinal thickness and histological analyses were performed to evaluate retinal edema, inflammation and implant biocompatibility respectively.
  
  
  RESULTS
  In Con A-induced inflammatory uveitic cataract model the BDI controlled anterior and posterior segment inflammation as well as retinal thickening more effectively than topical drops. The exposure (AUC0-t) of DXM with BDI is superior in all ocular tissues, while topical drops did not achieve therapeutic posterior segment levels and did not control inflammation nor prevent retinal edema and architectural disruption.
  
  
  CONCLUSIONS
  Our results demonstrate the superiority of the BDI in suppressing Con A-induced inflammation and retinal edema in NZW rabbits and highlight the need for sustained bidirectional delivery of potent anti-inflammatory agents for 5 to 6 weeks to optimize clinical outcomes.
authors.affiliation: Department of Ophthalmology, John A Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132, USA.
authors.forename: Srinivas Rao
authors.initials: SR
authors.lastname: Chennamaneni
authors.forename: Austin
authors.initials: A
authors.lastname: Bohner
authors.forename: Ashlie
authors.initials: A
authors.lastname: Bernhisel
authors.forename: Balamurali K
authors.initials: BK
authors.lastname: Ambati
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002386:Cataract / Q000139:chemically induced* / Q000188:drug therapy*; D003208:Concanavalin A / Q000494:pharmacology*; D003907:Dexamethasone / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D004487:Edema / Q000188:drug therapy; D005260:Female; D007249:Inflammation; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D009883:Ophthalmic Solutions; D003208:Concanavalin A; D003907:Dexamethasone