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Michael V W Bergamini, Tomas Navratil, Francesco Impagnatiello, Elena Bastia; Concomitant dosing of the NO-donor NCX 667 (1%) and Xalatan® (latanoprost ophthalmic solution 0.005%) results in robust and sustained IOP-lowering in ocular normotensive dogs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3193.
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Xalatan® (latanoprost ophthalmic solution, 0.005%) is the most commonly used ocular hypotensive prostaglandin analog (PGA). However, as for other PGAs, increasing doses (frequency or concentration) of latanoprost do not enhance its IOP-lowering efficacy. NCX 667 is a novel nitric oxide (NO)-donor shown to effectively reduce intraocular pressure (IOP) in various models of ocular hypertension and glaucoma. Furthermore, NCX 667 dosing in presence of a PGA resulted in sustained IOP reduction in rabbits. Here we compared the IOP-lowering effect of concomitant NCX 667 and Xalatan® to that of Xalatan® or NCX 667 alone in ocular normotensive dogs.
Male (n=4) and female (n=4) ocular normotensive Beagle dogs were included in the study. Test article groups were: vehicle (PBS pH 6, Cremophor EL 5%, DMSO 0.3%, BAC 0.02%), Xalatan®, NCX 667 (1%, dissolved in vehicle) or their concomitant dosing (Xalatan® first, followed by NCX 667 5 min later). The study was masked, cross-over with 1 week wash-out between individual experimental sessions. IOP was measured at each time point using a TonoVet®.
As expected, Xalatan® dosing resulted in a stable IOP lowering that became evident 120 min post-dosing (IOP change, -2.5±0.59 mmHg) and remained stable over time up to 24 hr (IOP changes, -2.4±0.80 mmHg). NCX 667 lowered IOP with a rapid onset (IOP change, -2.5±0.4 mmHg at 30 min post dose) that decayed over the following hour to reach baseline value at 120 min post-dose. Concomitant Xalatan® and NCX 667 dosing resulted in progressive IOP-lowering activity starting at 30 min (IOP changes, -3.8±0.96 mmHg) and reaching -3.1±0.84, -3.6±0.86, -3.6±0.74, & -3.4±0.71 mmHg respectively at 120, 240, 480, & 1440 min (24 hr) post-dosing.
Concomitant doing of Xalatan® and NCX 667 results in robust and sustained IOP-lowering in ocular normotensive dogs. Further studies are needed to establish the mechanism(s) of action involved and whether these effects translate into humans.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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