April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Tolerability and IOP Lowering Activity of a Topical Rho Kinase Inhibitor, ATS907, in Normotensive Rabbits
Author Affiliations & Notes
  • Henry H. Hsu
    Altheos, South San Francisco, California
  • Muralitharan Kengatharan
    Altheos, South San Francisco, California
  • H Umeno
    Research, Asahi Kasei Pharma, Tokyo, Japan
  • Barbara M. Wirostko
    Altheos, South San Francisco, California
  • Footnotes
    Commercial Relationships  Henry H. Hsu, Altheos (I, E, R); Muralitharan Kengatharan, Altheos (I, E, R); H. Umeno, Asahi Kasei Pharma (E, R); Barbara M. Wirostko, Altheos (I, C, R), Pfizer (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3109. doi:
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      Henry H. Hsu, Muralitharan Kengatharan, H Umeno, Barbara M. Wirostko; Tolerability and IOP Lowering Activity of a Topical Rho Kinase Inhibitor, ATS907, in Normotensive Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3109.

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

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Purpose: : To determine the tolerability and efficacy of a topically administered novel rho kinase (ROCK) inhibitor in normotensive (NT) rabbits.

Methods: : New Zealand White (NZW) rabbits (5 animals/group) received a single dose OD topically with ATS907 (0.02%, 0.05 & 0.2% ophthalmic formulation). OS served as the control. IOP was measured at baseline and 1, 2, 4, 6, 8, 10 and 12 hours post dose. A separate study investigated the effect of formulation pH on IOP following dosing 0.02 % ATS907 in saline solution, in which Japanese white rabbits received a single dose OS with the formulation pH adjusted from 4-9. IOP was measured at baseline and 2, 4, and 6 hours post dose. Tolerability was assessed in a separate 7-day dose ranging study in NZW rabbits with 0.1%, 0.3%, 0.5%, 1%, 3%, and 5% (ATS907 ophthalmic solution) administered topically BID. Gross exams and biomicroscopy was performed daily, ocular histopathology was performed on day 8.

Results: : ATS907 dose-dependently lowered IOP in rabbits. The maximum reduction in IOP produced by 0.02%, 0.05%, and 0.2% was -7.2 mmHg, -9.5 mmHg, and -11.0 mmHg, respectively, and occurred 1-2 hours post dose. Mean baseline IOP ranged from 23.3 mmHg to 25.4 mmHg per treatment arm. Increasing the pH enhanced the reduction in IOP. In the tolerability study, ATS907 was well tolerated at all doses up to 1%. Signs of mild-moderate conjunctival hyperemia seen with 3% & 5 % resolved within 2-4 hr of topical instillation. No significant effect was observed in corneal thickness, intraocular hemorrhages, pupillary response, or iris changes. There was no evidence of inflammation.

Conclusions: : ATS 907 ophthalmic solution was effective in rapidly lowering IOP after a single dose in a dose response manner in normotensive rabbits. Increasing the pH of the formulation enhanced IOP lowering. Tolerability profile was acceptable in all dose ranges with a noted increase in transient dose-related conjunctival hyperemia.

Keywords: outflow: trabecular meshwork • intraocular pressure 

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