Ocular Penetration and Pharmacokinetics of Ripasudil Following Topical Administration to Rabbits

Abstract

These results indicate favorable intraocular penetration characteristics of ripasudil following topical administration.

The Anti-Inflammatory Effect of Ripasudil (K-115), a Rho Kinase (ROCK) Inhibitor, on Endotoxin-Induced Uveitis in Rats

“…44 However, the present study administered the ROCK inhibitor systemically and did not investigate the topical administration of ripasudil, which is one of the limitations that should be further investigated in future studies. Because it has been previously reported that radiolabelled ripasudil reached the retina and choroid following the administration of eye drops in rabbits, 15,24 there are enough possibilities that topical administration of ripasudil could attenuate ocular inflammation both in the anterior and posterior segments of the eye. In the future studies, further investigation with topical and intravitreal administration will be required to verify these possible effects.…”

“…23 A previous study with the radiolabeled drug showed that ripasudil reached the retina and choroid after eye drop administration in rabbits. 15,24 However, it is not known if ripasudil treatment inhibits ocular inflammation in the anterior chamber or retina, and the role of the Rho/ROCK pathway in ocular inflammation and leukocyte adhesion in EIU has not yet been clarified. In the present study, we assessed the antiinflammatory properties of ripasudil in the rat EIU model and in LPS-stimulated mouse macrophage-like RAW264.7 cells.…”

Rho-Associated Protein Kinase Inhibitor Treatment Promotes Proliferation and Phagocytosis in Trabecular Meshwork Cells

“…The methods of ROCKi delivery may affect the site and mechanism of action. Repeated topical applications can achieve delivery of ROCKi drugs to both anterior and posterior segments, however, intravitreal, subconjunctival, and suprachoroidal injection methods may be more effective for delivery to posterior segment components, such as RGCs and optic nerve axons (Isobe et al, 2016;Pitha et al, 2018). Thus, we used subconjunctival injection to target TM cells, RGCs, and optic nerve axons.…”

Interaction Between Pilocarpine and Ripasudil on Intraocular Pressure, Pupil Diameter, and the Aqueous-Outflow Pathway

“…Ripasudil has been reported to bind strongly to melanin, and significantly higher ripasudil levels (approximately 16-fold those in the aqueous humor) have been observed in the iris-ciliary body of pigmented rabbits, even after a single instillation. 19 Therefore, it is possible that relaxation induced by ripasudil overcomes CM contraction induced by pilocarpine. The actual drug concentrations may differ in vivo; further studies are required to determine whether our in vitro observations are relevant in vivo.…”

“…The ripasudil concentrations in aqueous humor 30 to 60 minutes after a single instillation of ripasudil ophthalmic solution (1.0%, wt/vol) were approximately 10 lg/mL in the rabbit and 1 lg/mL in the monkey, corresponding to approximately 25 lM and 2.5 lM, respectively. 19 A previous report showed that the pilocarpine level in aqueous humor of the rabbit eye 30 to 60 minutes after 2% (wt/vol) pilocarpine instillation was 2.53 to 3.72 lg/mL, or approximately 92 lM. 20 In addition, we have preliminarily evaluated the concentrations of 1, 10, 30, 50, and 100 lM for both ripasudil and pilocarpine in in vitro studies and investigated the dose-response and maximal effects of each drugs, and then we determined the appropriate concentration of each drug.…”