Ocular Penetration and Pharmacokinetics of Ripasudil Following Topical Administration to Rabbits

Abstract Purpose: We evaluated the ocular pharmacokinetics of ripasudil (K-115), a selective Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, following topical administration to rabbits. Methods: We determined the ocular distribution of [14C]ripasudil by whole-head autoradiography and the radioactivity of each ocular tissue after single and multiple instillation of [14C]ripasudil to pigmented rabbits. We also measured the aqueous humor concentrations after concomitant instillation of ripasudil and a combination agent (0.005% latanoprost and 0.5% timolol) to pigmented rabbits as well as the tear fluid concentrations after instillation into rabbits, dogs, and monkeys using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Membrane permeability was evaluated using an in vitro parallel artificial membrane permeability assay system and Ussing chamber with rabbit cornea and conjunctiva. Results: [14C]Ripasudil was rapidly absorbed into the cornea and distributed throughout the eye...