June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Comparative IOP lowering from single dose studies of latanoprost, timolol and ONO-9054 in Dogs and Monkeys
Author Affiliations & Notes
  • Kazufumi Nagai
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Shinsaku Yamane
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Kazumi Moriyuki
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Tomohiro Karakawa
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Shintaro Nakao
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Tsutomu Shiroya
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Yutaka Shichino
    ONO PHARMACEUTICAL CO., LTD, Osaka, Japan
  • Footnotes
    Commercial Relationships Kazufumi Nagai, ONO PHARMACEUTICAL CO.,LTD (E); Shinsaku Yamane, ONO PHARMACEUTICAL CO., LTD. (E); Kazumi Moriyuki, ONO Pharmaceutical Co Ltd (E); Tomohiro Karakawa, ONO PHARMACETICAL CO., LTD (E); Shintaro Nakao, ONO Pharmaceutical Co.,LTD (E); Tsutomu Shiroya, ONO Pharmaceutical.Co.Ltd. (E); Yutaka Shichino, ONO Pharmaceutical Co Ltd (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1986. doi:
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      Kazufumi Nagai, Shinsaku Yamane, Kazumi Moriyuki, Tomohiro Karakawa, Shintaro Nakao, Tsutomu Shiroya, Yutaka Shichino; Comparative IOP lowering from single dose studies of latanoprost, timolol and ONO-9054 in Dogs and Monkeys. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1986.

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

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Abstract

Purpose: ONO-9054 (Ono Pharmaceuticals, Osaka Japan) is a novel prodrug compound. ONO-9054 is an isopropyl ester derivative of the free acid ONO-AG-367 that has been classified as a dual FP/EP3 agonist that may be effective in lowering intraocular pressure in humans. The purpose of this study was to investigate the effect of ONO-9054 on IOP in normotensive dogs and monkeys following a single ocular administration compared with that produced by latanoprost (a prostaglandin FP receptor agonist), timolol (a beta-adrenergic receptor antagonist) and a fixed combination of latanoprost / timolol.

Methods: IOP lowering effects of ONO-9054 (1, 3 and 10 µg/mL), latanoprost (50 µg/mL), timolol (5000 µg/mL) and a fixed latanoprost / timolol combination were examined in male beagle dogs. IOP was measured before and at 2, 4, 6, 8, and 24 hours after administration with an applanation pneumatonometer. In a second study the IOP lowering effect of ONO-9054 (0.1, 0.3, 1, 3, 10, 30 µg/mL) and latanoprost (50 µg/mL) were examined in male cynomolgus monkeys. The IOPs were measured before and at 4, 8, 12, 24, 48, 72 and 96 hours after administration. Compounds were administered topically in a 30 µL volume once into the right eye.

Results: In dogs, ONO-9054 lowered IOP in a dose-dependent manner, and the reduction of IOP persisted for at least 24 hours after administration. ONO-9054 at 3 µg/mL or more showed a more potent and longer-lasting reduction of IOP than latanoprost, ONO-9054 at 10 µg/mL showed more potent and longer-lasting reduction of IOP than the fixed latanoprost / timolol combination. In monkeys, ONO-9054 lowered IOP in a dose-dependent manner, and the reduction of IOP at 3 and 10 µg/mL was observed for up to 48 hours after administration and IOP at 30 µg/mL persisted for up to 72 hours after administration. The IOP reduction of ONO-9054 at 1 µg/mL was comparable to that of latanoprost and showed more potent and longer-lasting IOP-reducing effects at concentrations of 3 µg/mL or more.

Conclusions: The IOP-lowering effects of the FP/EP3 agonist ONO-9054 were more potent and longer-lasting than those produced by an FP receptor agonist, a beta-adrenergic receptor antagonist and a fixed combination FP agonist/beta-adrenergic antagonist. These results suggest that ONO-9054 should be considered further in clinical trials in patients with elevated intraocular pressure due to glaucoma.

Keywords: 568 intraocular pressure • 675 receptors: pharmacology/physiology  
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