June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Dose Based Pharmacokinetics of Sustained Release Dexamethasone in Beagles
Author Affiliations & Notes
  • Andrew Vanslette
    Ocular Therapeutix, Bedford, MA
  • Michael McGrath
    Ocular Therapeutix, Bedford, MA
  • Monica O'Connor
    Ocular Therapeutix, Bedford, MA
  • Charles D Blizzard
    Ocular Therapeutix, Bedford, MA
  • Ankita Desai
    Ocular Therapeutix, Bedford, MA
  • Michael Bassett
    Ocular Therapeutix, Bedford, MA
  • Peter K Jarrett
    Ocular Therapeutix, Bedford, MA
  • Arthur Driscoll
    Ocular Therapeutix, Bedford, MA
  • Amar Sawhney
    Ocular Therapeutix, Bedford, MA
  • Footnotes
    Commercial Relationships Andrew Vanslette, Ocular Therapeutix (E); Michael McGrath, Ocular Therapeutix (E); Monica O'Connor, Ocular Therapeutix (E); Charles Blizzard, Ocular Therapeutix (E); Ankita Desai, Ocular Therapeutix (E); Michael Bassett, Ocular Therapeutix (E); Peter Jarrett, Ocular Therapeutix (E); Arthur Driscoll, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 238. doi:
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      Andrew Vanslette, Michael McGrath, Monica O'Connor, Charles D Blizzard, Ankita Desai, Michael Bassett, Peter K Jarrett, Arthur Driscoll, Amar Sawhney; Dose Based Pharmacokinetics of Sustained Release Dexamethasone in Beagles. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):238.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To evaluate the effect of different incremental doses on the pharmacokinetic release profile of dexamethasone when delivered from a sustained release punctum plug (OTX-DP) in a preclinical animal model.

 
Methods
 

OTX-DP is a punctum plug containing dexamethasone within a biodegradable PEG hydrogel matrix. The hydrogel is conjugated with fluorescein to aid plug visualization. OTX-DP at three different doses (215, 581 and 718 µg per plug) were inserted into the inferior canaliculus of beagles (n=12 per group). Plug retention was assessed through the tissue using blue light with a yellow filter. Tear fluid samples were taken using a Schirmer test strip at predetermined time points and dexamethasone levels were analyzed in the strips by HPLC / MS.

 
Results
 

OTX-DP is designed to release dexamethasone into the tear fluid in a tapered profile, as shown in Figure One in the preclinical beagle model. The release of dexamethasone from the punctum plug is regulated by the limited solubility of the dexamethasone in the tear fluid at the interface of the proximal portion of the punctum plug within the canaliculus and by the concentration gradient which is initiated at that interface. A tapered drug release profile is created as the front of the concentration gradient recedes from the proximal portion of the punctum plug due to reduced drug levels. The duration of the drug release can therefore be controlled by regulating dose within the punctum plug, as shown in Figure Two.

 
Conclusions
 

Topical corticosteroids treat inflammation for several ophthalmic conditions. The dosing regimen may require multiple daily administrations followed by tapering to a lesser frequency as the inflammation subsides. A one-time administration of OTX-DP at different dosing levels, as demonstrated in the beagle model, can regulate the duration of therapy ensuring that dexamethasone treatment is delivered in a tapered drug release profile.  

 

 
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