AR-13324 is a potent inhibitor of ROCK I and ROCK II that has been shown to induce morphologic changes in cultured human and porcine TM cells at low concentration. AR-13324, a rho kinase inhibitor, and an inhibitor of the norepinephrine transporter, reduces intraocular pressure (IOP) in normotensive monkey eyes [1]. AR-13324 produces statistically significant lowering of EVP in DB rabbits [2].
The fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations [3]. AR-13324 0.02% was less effective than latanoprost by approximately 1 mmHg in patients with unmedicated IOPs in the range of 22 to 35 mmHg [4]
Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, the IOP measured by pneumatonometer in treated eyes was reduced (P< 0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes [1]. At 3 h postdosing, the reduction in EVP caused by AR-13324 treatment accounted for 42% of the measured reduction in IOP [2].
References:
[1].Wang RF, et al. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.
[2].Kiel JW, Kopczynski CC. Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits. J Ocul Pharmacol Ther. 2015 Apr;31(3):146-51.
[3].Lewis RA, Levy B, Ramirez N, et alFixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertensionBritish Journal of Ophthalmology 2016;100:339-344.
[4].Bacharach J, Dubiner HB, Levy B, Kopczynski CC, Novack GD; AR-13324-CS202 Study Group. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology. 2015 Feb;122(2):302-7.
AR-13324 是一种有效的 ROCK I 和 ROCK II 抑制剂,已被证明可在低浓度下诱导培养的人和猪 TM 细胞发生形态学变化。 AR-13324 是一种 rho 激酶抑制剂和去甲肾上腺素转运蛋白抑制剂,可降低血压正常的猴眼的眼内压 (IOP)[1]。 AR-13324 在 DB 兔 [2] 中产生具有统计学意义的 EVP 降低。
PG324 眼用溶液中 AR-13324 0.02% 和拉坦前列素 0.005% 的固定剂量组合在相同浓度下提供了临床和统计学上优于其单个活性成分的降眼压效果[3] . AR-13324 0.02% 比拉坦前列素低约 1 毫米汞柱,用于非药物眼压在 22 至 35 毫米汞柱范围内的患者 [4]
向 7 只正常猴眼单次给药 0.04% AR-13324 后 6 小时,与基线测量值相比,治疗眼中通过气压计测量的 IOP 降低 (P< 0.005) 25%,与基线测量值相比降低 24%对侧经载体处理的眼睛 [1]。给药后 3 小时,AR-13324 治疗引起的 EVP 降低占测得 IOP 降低的 42%[2]。