Elena Bastia, Francesco Impagnatiello, Ennio Ongini, Janet B Serle, Michael V W Bergamini; Repeated dosing of NCX 667, a new nitric oxide (NO) donor, retains IOP-lowering activity in animal models of glaucoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2106.
Purpose : NCX 667 is a novel NO-donor proven to effectively lower intraocular pressure (IOP) in rabbit and non-human primate models of glaucoma after single administration. Here we address the IOP-lowering effect of NCX 667 after repeated dosing.
Methods : NCX 667 (1%, 30μL dissolved in PBS with cremophor EL 5%, DMSO 0.3%, BAC 0.02%) was administered 4 consecutive times 1 hour apart within 1 day or bid (9AM & 4PM) for 5 days to ocular normotensive New Zealand White rabbits. IOPs were recorded prior to dosing and hourly post-dosing in the first study or 30, 60, 120, 180, and 240min post AM dose on days 1, 3 and 5 in the second study. Laser-induced ocular hypertensive non-human primates were treated bid (9AM & 4PM) for 5 consecutive days and IOPs measured hourly for 6 hours on days 1, 3 and 5. Two-way ANOVA followed by Bonferroni's multiple comparison test was performed as statistical analysis.
Results : In rabbits, NCX 667 resulted in sustained IOP-lowering when administered hourly during 4h (IOP change= -3.11 ± 0.72 and -3.11± 0.74 mmHg, 30-60 min following the first and the fourth administration, respectively). Similarly, on day 1, NCX 667 AM dose rapidly lowered IOP (IOP change= -3.6 ± 1.0 mmHg, p<0.05 vs. vehicle at 30min), and slowly returned to baseline values of 21.2 ± 0.2 mmHg at 240min. NCX 667 was as effective on day 3 (IOP change= -2.7 ± 0.4 mmHg, 30min) and 5 (IOP change= -3.9 ± 0.5 mmHg, 30min) compared to day 1. No signs of ocular discomfort were observed. Similarly, in the primates NCX 667 retained its IOP-lowering effects over 5 days of treatment (IOP change= -8.5 ± 5.6 mmHg, day 1 and -8.6 ± 4.5 mmHg, day 5).
Conclusions : Regardless of the experimental paradigm used, repeated dosing with NCX 667 resulted in comparable IOP-lowering activity over time with no signs of tachyphylaxis or ocular discomfort.