title: Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study.
abstract: OBJECTIVE
  To investigate the intra-ocular pressure (IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
  
  
  METHODS
  In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline.
  
  
  RESULTS
  The mean IOP reduction was -5.2 mmHg for 0.2%, -6.4 mmHg for 0.4% and -2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were -6.8 mmHg for 0.2%, -7.3 mmHg for 0.4% and -4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo.
  
  
  CONCLUSIONS
  Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT.
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Ophthalmology, Osaka Kosei Nenkin Hospital, Osaka, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kuwayama
authors.affiliation: The Division of Ophthalmology & Visual Science, Niigata University Medical & Dental Hospital, Niigata, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Kowa Company, Ltd, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Suganami
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D011446:Prospective Studies; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; C584679:K-115; D013449:Sulfonamides; D054460:rho-Associated Kinases
keywords: K-115; Rho kinase inhibitor; glaucoma; intra-ocular pressure; ripasudil