September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
IOP-lowering effects of NCX 667 in combination with travoprost in ocular normotensive and transient hypertensive rabbits
Author Affiliations & Notes
  • Elena Bastia
    Nicox Research Institute, Bresso (MI), Italy
  • Emanuela Masini
    NEUROFARBA, Section of Pharmacology and Toxicology, Firenze, Italy
  • Mariaconcetta Durante
    NEUROFARBA, Section of Pharmacology and Toxicology, Firenze, Italy
  • Michael V.W. Bergamini
    Nicox Ophthalmics Inc., Fort Worth, Texas, United States
  • Ennio Ongini
    Nicox Research Institute, Bresso (MI), Italy
  • Francesco Impagnatiello
    Nicox Research Institute, Bresso (MI), Italy
  • Footnotes
    Commercial Relationships   Elena Bastia, Nicox Research Institute (E); Emanuela Masini, Nicox Research Institute (F); Mariaconcetta Durante, None; Michael V.W. Bergamini, Nicox Ophthalmics Inc. (E); Ennio Ongini, Nicox Reasearch Intitute (C); Francesco Impagnatiello, Nicox Reasearch institute (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3031. doi:
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      Elena Bastia, Emanuela Masini, Mariaconcetta Durante, Michael V.W. Bergamini, Ennio Ongini, Francesco Impagnatiello; IOP-lowering effects of NCX 667 in combination with travoprost in ocular normotensive and transient hypertensive rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3031.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : NCX 667 is a novel stand-alone nitric oxide (NO)-donor previously shown to potently and effectively lowers intraocular pressure (IOP) in preclinical animal models of ocular hypertension and glaucoma; however, the IOP-lowering potential of NCX 667 was not investigated in concomitant administration with existing therapeutics. Here we report on the IOP-lowering effects of NCX 667 alone and combined with clinically relevant doses of the prostaglandin F2α (PGF2α) analogue travoprost in rabbits.

Methods : New Zealand white (NZW) rabbits with transient hypertonic saline-induced IOP elevation (tOHT-rabbits) and ocular normotensive NZW rabbits were used. In tOHT-rabbits, 0.1 ml of saline solution (5%) was injected into the vitreous humor of both eyes. IOP was measured prior to (baseline) and during the following 5hrs post-dosing. In both animal models two treatment schedules were followed: dosing NCX 667 10 min before travoprost; and dosing NCX 667 10 min after travoprost.

Results : As expected in ocular normotensive rabbits, travoprost (0.004%, 30μl) showed minimal IOP lowering (Emax= -1.6±1.6 mmHg at 30 min) whereas 0.1% of NCX 667 was selected as the minimal effective dose (Emax= -2.1±0.4 mmHg at 60 min). NCX 667 (0.1%, 30μl) combined with travoprost (0.004%, 30μl) resulted in superior efficacy (Emax= -3.9±0.8, -2.1±0.4 and -1.6±1.6 mmHg for NCX 667+travoprost, NCX 667 and travoprost, respectively). Surprisingly, the combination of NCX 667 and travoprost resulted in steady IOP-lowering up to 5hrs post-dosing not otherwise recorded for the compounds administered alone (E5hrs= -2.6±0.7, 1.1±0.8 and -0.6±0.1 mmHg for NCX 667+travoprost, NCX 667 and travoprost, respectively). Similar results were obtained when NCX 667 was administered after travoprost. In tOHT-rabbits, NCX 667 (0.3%, 30μl) combined with travoprost (0.004%, 30μl) resulted in superior IOP-lowering efficacy compared to each drug given alone. Due to the transient nature of the in tOHT-rabbit model the duration of the IOP-lowering activity could not be assessed.

Conclusions : NCX 667 is an effective IOP-lowering agent whose efficacy is not only strengthened but also prolonged when combined with the PGF2α agonist travoprost. Additional investigations are needed to better understand the mechanism of action involved.

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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