September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Comparative Ocular Distribution of 14C-Latanoprost Following a Single Intracameral or Repeated Topical Ocular Dose in Dogs
Author Affiliations & Notes
  • Jie Shen
    Allergan, Irvine, California, United States
  • Michael R Robinson
    Allergan, Irvine, California, United States
  • Mayssa Attar
    Allergan, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Jie Shen, Allergan (E); Michael Robinson, Allergan (E); Mayssa Attar, Allergan (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5640. doi:
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    • Get Citation

      Jie Shen, Michael R Robinson, Mayssa Attar; Comparative Ocular Distribution of 14C-Latanoprost Following a Single Intracameral or Repeated Topical Ocular Dose in Dogs. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5640.

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

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Abstract

Purpose : To assess the ocular distribution of 14C-lantanoprost following a single intracameral (IC) or repeated topical ocular administration to beagle dogs.

Methods : Purebred male beagle dogs were assigned to 2 study groups (N=3 per group). Group 1 received a once daily bilateral dose of 14C-latanoprost for 5 days and Group 2 received a single bilateral IC dose of 14C-latanoprost. Animals in Group 1 were euthanized at 1, 4, and 24 hours post last dose and animals in Group 2 were euthanized at 1, 2, and 4 hours postdose. Serial cross-sections of the eyes were collected at a thickness of 40 μm at intervals of 0.5 mm and processed for autoradioluminography (ARL). Sections for ARL were collected onto non-coated glass slides and exposed to a phosphor imaging plate.

Results : The ARL analysis showed that majority of the radioactivity for IC dosing to be localized in the anterior chamber of the eye at all time points; whereas, for topical dosing it was more diffused throughout the eye. Significantly higher radioactivity levels were achieved in the cornea (~6X), ciliary body (~40X), and iris (~15X) across all timepoints for the IC route as compared to the topical route. Higher conjunctival exposure was observed in both the palpebral (~5X) and bulbar conjunctiva (~1.5X) at 1 hour post dose for the topical dosing route. The topical administration also showed more radioactivity in the eyelids and orbital fat. Both dosing routes resulted in negligible drug distribution to the posterior eye including the retina.

Conclusions : Comparing the two dosing routes, IC delivery can result in a more localized delivery to the anterior chamber, with higher target tissue drug exposure consistent with the lack of a physical barrier for drug diffusion when compared to topical ocular dose route. In addition, with lower drug exposure to the conjunctiva and the ocular adnexa with IC dosing, this route of administration has the potential to reduce adverse effects such as conjunctival hyperemia and orbital fat atrophy reported with topical administration of prostaglandin and prostamide.

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

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