24h IOP control by subchronic AMA0076 administration in Dutch Belted rabbits

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AbstractPurpose To investigate IOP lowering efficacy of rho kinase (ROCK) inhibitors, AMA0076 and Y‐39983, after subchronic treatment.Methods Dutch Belted rabbits (5 rabbits/concentration) were treated daily with a single topical dose of AMA0076 (0.05, 0.1 and 0.4%) or Y‐39983 (0.025, 0.05 and 0.1%) in a masked fashion for 14 days. Saline was used as control in the contralateral eye. IOP was measured before, 3 and 7 hours after administration of the treatment. AMA0076 is a locally acting ROCK inhibitor, to reduce side effects such as hyperemia otherwise seen after administration of a ROCK inhibitor.Results Mean baseline IOP before the start of the experiment was 21.02 ± 0.42 and 20.69 ± 0.39 mmHg for AMA0076 and Y‐39983, respectively. Significant IOP reduction was observed in all AMA0076 and Y‐39983 treatment groups. A maximal IOP reduction of 39 and 35% was reached with AMA0076 0.1% and Y‐39983 0.05%, respectively. Initially, IOP returned to baseline values 24h after administration of AMA0076. After 3 days of treatment with AMA0076 a sustained IOP lowering effect was present, IOP did not return to baseline values, but remained significantly lower for all concentrations of AMA0076 (p<0.05). Treatment with Y‐39983 did not show this sustained IOP decrease. As a result of this sustained IOP lowering effect smaller IOP fluctuations were observed in animals treated with AMA0076 compared to Y‐39983. Hyperemia was observed with all concentrations of Y‐39983 whereas only mild hyperemia was induced after administration of AMA0076 0.4%.Conclusion Once daily treatment of rabbits with ROCK inhibitor AMA0076 resulted in IOP reduction that was more sustained and associated with smaller peak‐through fluctuations than Y‐39983.