June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Pharmacokinetics of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits
Author Affiliations & Notes
  • Tim Jarrett
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Rami F Elhayek
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Zach Lattrell
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Michael McGrath
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Stephen Takach
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Peter K Jarrett
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Jonathan H. Talamo
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Amar Sawhney
    Ocular Therapeutix, Bedford, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Tim Jarrett, Ocular Therapeutix (E); Rami Elhayek, Ocular Therapeutix (E); Zach Lattrell, Ocular Therapeutix (E); Michael McGrath, Ocular Therapeutix (E); Stephen Takach, Ocular Therapeutix (E); Peter Jarrett, Ocular Therapeutix (E); Jonathan Talamo, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support  Ocular Therapeutix supported this research.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1984. doi:
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    • Get Citation

      Tim Jarrett, Rami F Elhayek, Zach Lattrell, Michael McGrath, Stephen Takach, Peter K Jarrett, Jonathan H. Talamo, Amar Sawhney; Pharmacokinetics of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in Dutch Belted Rabbits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1984.

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

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Abstract

Purpose : We evaluated the pharmacokinetics over 6 months of sustained delivery of a tyrosine kinase inhibitor (TKI) with known anti-angiogenic properties from a preformed bioabsorbable hydrogel fiber depot delivered via intravitreal injection in Dutch belted rabbits.

Methods : Micronized TKI particles were formulated in a hydrogel matrix (OTX-TKI). Eighteen eyes of naïve Dutch belted rabbits (n=9) were bilaterally dosed with OTX-TKI at Day 0 and were enucleated and flash frozen at Months 1 (n=12), 3 (n=18) and 6 (n=18). Plasma, aqueous humor, vitreous humor, retina and choroid were collected then analyzed by high performance liquid chromatography for tissue concentration.

Results : OTX-TKI produced significant levels of TKI in the vitreous humor, retina and choroid at 1, 3 and 6 months. High levels (>3800x IC50) of TKI were recorded in the vitreous humor, retina and choroid from Month 1 through 6 without clinical evidence of local toxicity. The observed concentrations of TKI increased over time in these tissues. TKI was below the level of quantification (<0.015 ng/mL) in the aqueous humor and plasma at all time points.

Conclusions : We have demonstrated for the first time the ability to deliver and maintain high tissue levels of TKI in vitreous humor, retina, and choroid using an intravitreal bioabsorbable hydrogel depot for 6 months. Tissue concentrations were highest at 6 months; this observation may reflect a somewhat higher TKI release rate at the termination of the depot lifetime. Plasma levels were below the level of quantification, suggesting minimal risk of systemic toxicity.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Relationship of Drug Exposure of OTX-TKI over Time

Relationship of Drug Exposure of OTX-TKI over Time

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