title: Ocular hypotensive effect of tafluprost in latanoprost low-responder cynomolgus monkeys.
abstract: OBJECTIVE
  To determine the proportion of latanoprost low-responders among cynomolgus monkeys, and to evaluate the switching efficacy from latanoprost to tafluprost in latanoprost low-responder monkeys.
  
  
  METHODS
  Thirty-nine ocular normotensive monkeys were used in this study. Latanoprost low-responders were detected using a 2-step evaluation procedure. In the first step, the response to single administration of latanoprost was investigated in all monkeys. In the second step, the response to 7-day administration of latanoprost was evaluated in screened monkeys. We defined latanoprost low-responders as any monkey that showed intraocular pressure (IOP) reduction of 1 mm Hg or less during the 7-day treatment. Switching efficacy from latanoprost to tafluprost was then evaluated in a 3-phase switching study. Latanoprost was topically administered for about 1 week in phases 1 and 3, with tafluprost being topically administered for about 1 week in phase 2.
  
  
  RESULTS
  Eleven monkeys were "latanoprost low-responders." The maximal IOP reduction exhibited by these low-responders in the second step of the evaluation was 0.5±0.2 mm Hg (mean±SEM) during saline treatment and 0.8±0.2 mm Hg during latanoprost treatment. In the 3-phase switching study, the maximal IOP reductions were: 0.4±0.2 mm Hg in phase 1 (latanoprost), 2.4±0.3 mm Hg in phase 2 (tafluprost), and 0.5±0.2 mm Hg in phase 3 (latanoprost).
  
  
  CONCLUSIONS
  Latanoprost low-responders exist among cynomolgus monkeys. Switching from latanoprost to tafluprost reduced IOP, and tafluprost's IOP-lowering effect disappeared after switching back to latanoprost in the latanoprost low-responder monkeys. These results suggested that tafluprost might be effective for latanoprost nonresponder patients.
authors.affiliation: Research and Development Center, Santen Pharmaceutical Co., Ltd, Nara, Japan. hiroaki.kurashima@santen.co.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kurashima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Asai
authors.forename: Makoto
authors.initials: M
authors.lastname: Aihara
authors.forename: Naruhiro
authors.initials: N
authors.lastname: Ishida
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D057915:Drug Substitution; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D015814:Ocular Hypotension / Q000188:drug therapy*; D011460:Prostaglandins F / Q000008:administration & dosage*; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D014065:Tonometry, Ocular
chemical_list: D000959:Antihypertensive Agents; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; C485333:tafluprost; D000077338:Latanoprost