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• W3131010489 abstract "Purpose: We studied the IOP-lowering effects of NCX 1741, a novel nitric oxide (NO)-donating derivative of the phosphodiesterase type-5 inhibitor, avanafil, in Cynomolgus monkey with laser-induced ocular hypertension (OHT-monkeys). NCX 1193 (NO-donating moiety), NCX 1744 (NCX 1741 without ester nitrate moiety), and travoprost (PGF2α analogue) were used for comparison. Ocular exposure after NCX 1741 dosing also was addressed. Methods: Vehicle (phosphate buffer pH 6.0, Kolliphor® 5%, DMSO 0.3%, benzalkonium chloride 0.02%), NCX 1741, NCX 1193, NCX 1744, or travoprost were instilled (30 μL; single dose) masked and conscious IOPs were measured by pneumatonometry. LC-MS/MS-based methods were employed to monitor ocular exposure of NCX 1741 and main metabolites after ocular dosing in New Zealand White rabbits. Results: NCX 1741 (2.2%, 0.8 μmol/eye) lowered IOP with an Emax (ΔΔIOP, IOP change vs. pre-dose and vehicle) between 5 and 8 h post-dosing (ΔΔIOP5h, −5.3 ± 2.0 mmHg and ΔΔIOP8h, −6.0 ± 2.1 mmHg). Conversely, equimolar (0.47%, 0.8 μmol/eye) NCX 1193 IOP-lowering effects were maximal 3 h post-dosing (ΔΔIOP3h, −4.7 ± 1.6 mmHg) and declined thereafter (ΔΔIOP5h, −1.6 ± 1.1 mmHg). In a follow-up study, NCX 1741 (1.5%, 0.5 μmol/eye) was more effective than NCX 1744 despite a similar duration. Further, NCX 1741 was as effective as travoprost (0.1%, 0.06 μmol/eye) at 5 and 8 h post-dosing (travoprost, ΔΔIOP5h, −3.4 ± 2.2 mmHg and ΔΔIOP8h, −4.9 ± 1.3 mmHg) but had shorter duration (NCX 1741, ΔΔIOP24h, −1.5 ± 1.1 mmHg; travoprost, ΔΔIOP24h, −7.1 ± 2.8 mmHg). NCX 1741 resulted in significant aqueous humor exposure, as determined by the levels of the main metabolite, avanafil. Conclusions: NCX 1741 rapidly and effectively lowers IOP in OHT-monkeys for several hours post-dosing. How these effects translate in humans is still to be defined." @default.
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• W3131010489 date "2021-05-01" @default.
• W3131010489 modified "2023-09-27" @default.
• W3131010489 title "NCX 1741, a Novel Nitric Oxide-Donating Phosphodiesterase-5 Inhibitor, Exerts Rapid and Long-Lasting Intraocular Pressure-Lowering in Cynomolgus Monkeys" @default.
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• W3131010489 doi "https://doi.org/10.1089/jop.2020.0126" @default.
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