Abstract
Purpose :
Rhopressa® (0.02% netarsaudil), a novel rho-kinase (ROCK) inhibitor and norepinephrine transporter inhibitor, has been approved for lowering intraocular pressure (IOP) of glaucoma. We evaluated the IOP-lowering effects of this drug in normotensive rabbit, dog, and monkey eyes for comparison.
Methods :
Adult naïve Chinchilla rabbits (n=24), Beagle dogs (n=14) and Cynomolgus monkeys (n=12) were used in the study. Animals of each species were randomly and evenly divided into two groups with mixed genders. Rhopressa® (30 µl) was topically administered unilaterally onto one eye and the contralateral eye of each individual was treated with the same volume of normal saline. The dosing regimen was once daily for 3 consecutive days in the rabbit and monkey studies and was only one dose in the dog study. Conscious IOP was measured with an ICARE® TONOVET Plus in rabbits and dogs and a Reichert 30 pneumatonometer in monkeys at 0 (prior to dosing), 0.5, 2, 4, 6, 24h after the 1st and the 3rd dose in rabbits and monkeys (48h IOP was added after the 3rd dosing in monkey study), and 0, 1, 2, 4, 6, 8, 24h after the treatment in dogs.
Results :
Compared to the vehicle treated eyes, Rhopressa® significantly (p< 0.05) reduced rabbit IOP during 2-6h after the 1st and the 3rd dosing, and its effect was more apparent after the third dosing. The maximal IOP reduction was -23.6±7.5% (Mean±SD) at 4h post the 1st dosing and -25.7±8.3% at 2h after the 3rd dosing. Compared with the rabbit, Rhopressa® caused more robust and prolonged IOP reduction in monkey eyes. Maximal IOP reduction was -37.1±12.1% at 6h after the 3rd dosing. Significant (p< 0.05) IOP reduction lasted from 2h through 24h after the 1st and the 3rd dosing. In Beagle dogs, however, only a mild and non-significant IOP reduction was observed 2-6 h after dosing.
Conclusions :
Rhopressa® significantly lowered IOP in normotensive eyes of Chinchilla rabbits and Cynomolgus monkeys, which can be considered as primary models for pre-clinical efficacy study of ROCK inhibitors.
This is a 2020 ARVO Annual Meeting abstract.