September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Sustained Retinal Concentrations of OHR3031 Achieved with Intravitreal Injection of a Biodegradable Microparticle Formulation to Rabbits
Author Affiliations & Notes
  • Marlene Woodruff Modi
    Ohr Pharmaceutical, New York, New York, United States
  • Barbara M Wirostko
    Ohr Pharmaceutical, New York, New York, United States
  • Robert Jennings
    Ohr Pharmaceutical, New York, New York, United States
  • Laxma Reddy
    Ohr Pharmaceutical, New York, New York, United States
  • Nikita Malavia
    Ohr Pharmaceutical, New York, New York, United States
  • Alisha Simonian
    Ohr Pharmaceutical, New York, New York, United States
  • Istvan Szinai
    Ohr Pharmaceutical, New York, New York, United States
  • Glenn Stoller
    Ohr Pharmaceutical, New York, New York, United States
  • Footnotes
    Commercial Relationships   Marlene Modi, Ohr Pharmaceutical, Inc. (C); Barbara Wirostko, Ohr Pharmaceutical, Inc. (C); Robert Jennings, Ohr Pharmaceutical, Inc. (E); Laxma Reddy, Ohr Pharmaceutical, Inc. (E); Nikita Malavia, Ohr Pharmaceutical, Inc. (E); Alisha Simonian, Ohr Pharmaceutical, Inc. (E); Istvan Szinai, Ohr Pharmaceutical, Inc. (E); Glenn Stoller, Ohr Pharmaceutical, Inc. (S)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 770. doi:
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      Marlene Woodruff Modi, Barbara M Wirostko, Robert Jennings, Laxma Reddy, Nikita Malavia, Alisha Simonian, Istvan Szinai, Glenn Stoller; Sustained Retinal Concentrations of OHR3031 Achieved with Intravitreal Injection of a Biodegradable Microparticle Formulation to Rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):770.

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

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Abstract

Purpose : Intravitreal (IVT) injections provide high doses of anti-VEGF (vascular endothelial growth factor) agents to the eye with few or no systemic side effects. However, frequent IVT injections are needed for optimal efficacy of anti-VEGF agents in many patients. The study aim was to achieve sustained therapeutic concentrations of a small molecule anti-angiogenic compound, OHR3031, after IVT injection of a biodegradable drug delivery system. Targeted therapeutic concentrations were established from in vitro studies of inhibition of proliferation of cultured human retinal microvascular endothelial cells.

Methods : Nine male New Zealand White rabbits aged 5 months received bilateral IVT injections of 2.6 mg OHR3031 on Day 0. Inferior injections were administered at about 6 o’clock. At specified times up to 42 days post dosing, 1 animal was euthanized per time point, eyes harvested and flash frozen, and plasma collected for bioanalysis. A qualified liquid chromatography-tandem mass spectrometry and noncompartmental pharmacokinetic methods were used to quantify and summarize ocular tissue and plasma concentrations of OHR3031 and active metabolite.

Results : After IVT injection, an ocular tissue concentration gradient of OHR3031 was observed (vitreous > retina ≥ choroid ≥sclera > iris-ciliary body ≈ aqueous humor; Figure 1). Sustained delivery of OHR3031 was shown based on the sustained vitreous concentrations seen over 42 days. As vitreous concentrations did not decline, sustained delivery was likely longer. Given supratherapeutic concentrations of active metabolite were present in the retina and choroid, this suggests active metabolite is continually formed from the parent OHR3031. Lower OHR3031 aqueous humor concentrations indicated most of the dose distributed posteriorly to the retina. Very low plasma concentrations were seen over 42 days.

Conclusions : Sustained supratherapeutic concentrations of OHR3031 were achieved in target ocular tissues after a single IVT injection of a biodegradable drug delivery system for at least 6 weeks.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

OHR3031 ocular tissue conc (ng/g or ng/mL) versus time in days post injection. Legend: Symbol-each eye, Line-average of both eyes, Vitreous humor-black, Retina-green, Choroid-orange, Sclera-red, Aqueous humor-purple, Iris-ciliary body-aqua

OHR3031 ocular tissue conc (ng/g or ng/mL) versus time in days post injection. Legend: Symbol-each eye, Line-average of both eyes, Vitreous humor-black, Retina-green, Choroid-orange, Sclera-red, Aqueous humor-purple, Iris-ciliary body-aqua

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