April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Role Of Ocular Pigmentation In The Intraocular Pressure Response To Brimonidine In Rabbits
Author Affiliations & Notes
  • James A. Burke
    Biological Sciences, Allergan Inc, Irvine, California
  • Lupe Ruiz
    Biological Sciences, Allergan Inc, Irvine, California
  • Barbara Feldmann
    Biological Sciences, Allergan Inc, Irvine, California
  • Werhner Orilla
    Biological Sciences, Allergan Inc, Irvine, California
  • Corine Ghosn
    Biological Sciences, Allergan Inc, Irvine, California
  • Louis Lo
    Biological Sciences, Allergan Inc, Irvine, California
  • Jinsong NI
    Biological Sciences, Allergan Inc, Irvine, California
  • Jie Shen
    Biological Sciences, Allergan Inc, Irvine, California
  • Larry Wheeler
    Biological Sciences, Allergan Inc, Irvine, California
  • Footnotes
    Commercial Relationships  James A. Burke, Allergan, Inc. (E); Lupe Ruiz, Allergan, Inc. (E); Barbara Feldmann, Allergan, Inc. (E); Werhner Orilla, Allergan, Inc. (E); Corine Ghosn, Allergan, Inc. (E); Louis Lo, Allergan, Inc. (E); Jinsong Ni, Allergan, Inc. (E); Jie Shen, Allergan, Inc. (E); Larry Wheeler, Allergan, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2466. doi:
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      James A. Burke, Lupe Ruiz, Barbara Feldmann, Werhner Orilla, Corine Ghosn, Louis Lo, Jinsong NI, Jie Shen, Larry Wheeler; The Role Of Ocular Pigmentation In The Intraocular Pressure Response To Brimonidine In Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2466.

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

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Abstract

Purpose: : Drug binding to ocular melanin is thought to play a role in the efficacy of ocular hypertensive therapy. Brimonidine (BRI), the active ingredient in Alphagan®, binds with high affinity to ocular melanin (IOVS 1992;33:1015) and when dosed topically, results in higher drug concentrations in the iris/ciliary body of pigmented rabbits compared to albino rabbits (Drug Metab Dispos. 2002;30:421-429). The purpose of this study was to compare the IOP response to BRI in pigmented and albino rabbits following topical and intracameral (IC) administration. IC dosing ensures, at least initially, equivalent drug exposure to the epithelial layer of the ciliary body, the purported site of action. Aqueous humor (AH) drug concentrations were also assessed as an inference for drug sequestration into melanin-containing tissues.

Methods: : Twenty one New Zealand White (albino) and 21 Dutch-Belted (pigmented) rabbits weighing ~ 2.5 kg were used in this study. Eighteen animals from each strain were dosed in OS with topical 0.15%, 35ul BRI, and in OD with IC 5 ug, 20 ul brimonidine, after a 2-week washout. Other animals were dosed with saline. Follow-up for IOP was at 0, 0.5, 1, 2, 4, 6, 24 and 48 hrs. Additionally, 50 ul of AH was removed at 0.5, 1, 2, 4, 6 and 24 hrs in 3 rabbits per timepoint and assayed for [BRI] using liquid chromatography-mass spectrometry/mass spectrometry methods. IOP of eyes with paracenthesis were not evaluated at subsequent timepoints, but were included at the 48 hrs follow-up.

Results: : Pigmented rabbits had higher baseline IOPs than albino rabbits. IOP was 29.1 ± 0.1 mm Hg in pigmented eyes (n=18) and 17.6 ± 0.5 mm Hg in albino eyes (n=18) for the topical dosing study and were similar for the IC dosing study. Topical BRI decreased IOP more in pigmented eyes from 0.5 - 2 hrs, and less from 4 - 6 hrs. For example, at 1 hr, IOP decreased 25 ± 3% (n=15) and 8 ± 4% (n=15) in pigmented eyes and albino eyes respectively (p<0.05); at 6 hrs, IOP decreased 9 ± 6% (n=6) and 17 ± 4% (n=6) in pigmented and albino eyes, respectively (p<0.05). IC BRI decreased IOP more in pigmented eyes from 0.5 - 6 hours. The peak response was at 1 hr: -46 ± 2% (n=15) in pigmented eyes and -31 ± 4% (n=15) in albino eyes (p<0.05). AH [BRI] was not statistically different between pigmented and albino eyes for both topical and IC dosing, but tended to be lower in pigmented eyes. For topical dosing, AUC0-t (ng.hr/ml) were 2270 ± 200 and 2650 ± 490 in pigmented and albino eyes, respectively; and were 16400 ± 700 and 17500 ± 1300, respectively for IC dosing.

Conclusions: : Ocular melanin facilitates a larger IOP response to BRI.

Keywords: intraocular pressure • melanocytes 
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