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Sonja Kroesser, Elizabeth Spencer, Ralf Grillenberger, Craig B Struble, Kirsten Fischer; Ocular and Systemic Distribution of 14C- Perfluorohexyloctane following Topical Ocular Administration to Rabbits. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2656. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Perfluorohexyloctane a semifluorinated alkane, which is now in Phase 2 clinical investigations in the US, is developed as an ocular treatment for the signs and symptoms of evaporative Dry Eye Disease. This is due to its excellent spreading and film-forming properties that strengthen the lipid layer of the tear film thereby preventing excessive evaporation of the aqueous layer of the tear film. Ocular and systemic distribution studies after topical ocular administration of 14C-Perfluorohexyloctane in rabbits were conducted to further characterize the compound.
Female pigmented rabbits received a bilateral single topical ocular dose of 14C-Perfluorohexyloctane twice daily for 4 days and once on day 5, at a targeted dose level of 45.6 mg/eye. Before euthanasia on Day 5, tears were collected. Blood and ocular tissues were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after the last dose and all samples were analyzed for radioactivity.
After ocular administration Perfluorohexyloctane was detected in the ocular tissues in the following order: tears > meibomian glands > cornea > palpebral conjunctiva > lacrimal glands > bulbar conjunctiva. Exposure in the anterior ocular tissues was considerably higher compared to very low levels sporadically detected in the intraocular tissues (vitreous humor, choroid-RPE, and retina). Interestingly, the high levels in tears were maintained for a minimum of 4 hours. In meibomian glands significant levels were seen up to 8 hours. Systemic exposure in blood and plasma was low after single and repeated doses of radiolabeled 14C-Perfluorohexyloctane, indicating a low level of systemic absorption and no accumulation after repeated topical ocular administration.
Highest exposure and longest presence of Perfluorohexyloctane in rabbit was seen in anterior ocular tissues, especially tears and meibomian glands. In particular the high levels of Perfluorohexyloctane in the meibomian glands support the potential for treatment of meibomian gland dysfunction associated with dry eye syndrome as it may solubilize the meibom within the glands.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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