Document Detail


Pharmacokinetics and Efficacy of Bioerodible Dexamethasone Implant in Concanavalin A-induced Uveitic Cataract Rabbit Model.
MedLine Citation:
PMID:  24947436     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: 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:
Srinivas Rao Chennamaneni; Austin Bohner; Ashlie Bernhisel; Balamurali K Ambati
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-20
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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