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. 2018 Mar 1;34(1-2):40–51. doi: 10.1089/jop.2017.0023

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© Cheng-Wen Lin et al. 2018; Published by Mary Ann Liebert, Inc.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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FIG. 6. — Metabolism of netarsudil by ocular tissues. (A) Metabolism of netarsudil in the presence of corneal tissue isolated from Dutch Belted rabbit (n = 3), beagle dog (n = 3), pig (n = 3), cynomolgus monkey (n = 4), and human (n = 3) corneas. Corneal metabolism assays were initiated by adding netarsudil in assay buffer to wells containing individual corneal punches in assay buffer followed by incubation at 37°C. Samples were removed at specified time intervals and analyzed by HPLC to determine the percentage of netarsudil remaining at each time point. (B) Levels of netarsudil versus netarsudil-M1 in AH following topical ocular application of netarsudil 0.02% to Dutch Belted rabbits. Netarsudil was administered to both eyes of 3 male New Zealand rabbits in each of 4 groups. In groups 1 and 2, test article was dosed only once, and samples of AH were taken from each eye by paracentesis at 4 or 6 h postdose, respectively. In groups 3 and 4, test article was dosed once daily for 3 or 4 days, respectively, and samples of AH were taken 4 h after dosing. Levels of netarsudil and its metabolite netarsudil-M1 were measured in the samples by HPLC/mass spectrometry. AH, aqueous humor; HPLC, high performance liquid chromatography.