title: Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers.
abstract: OBJECTIVE
  To evaluate the ocular hypotensive efficacy, ocular and systemic safety, and systemic exposure of two formulations of 0.5% AR-12286 Ophthalmic Solution.
  
  
  METHODS
  This was a double-masked, single-centre, crossover study in 18 normal adult volunteers. Volunteers were randomised to one of two dosing sequences: Formulation A once daily, both eyes (OU) for 8 days, a 7-day minimum washout, and then Formulation B, or the reverse. The main outcome measures were ocular tolerability, intraocular pressure (IOP) and blood levels of AR-12286 and its metabolites.
  
  
  RESULTS
  Systemic absorption was low, with a majority of subjects showing no measurable drug concentration in plasma (<1 ng/ml) at any time point with either formulation. The most frequent ocular adverse events were conjunctival hyperaemia, eye irritation, instillation site reaction, increased lacrimation, and blurred vision which were relatively short-lived and judged as not clinically significant. Both formulations of AR-12286 produced substantial reductions from baseline IOP ranging from 3 to 7 mm Hg (p<0.0001).
  
  
  CONCLUSIONS
  No differences were noted in ocular safety between formulations of AR-12286 0.5%, dosed once daily in the morning for 8 days. AR-12286 produced little systemic exposure to the parent compound or two known metabolites. Clinically and statistically significant reductions in IOP were seen in these normotensive subjects.
authors: Department of R&D, Aerie Pharmaceuticals, Inc., Bridgewater, NJ, USA.
authors: Casey
authors: C
authors: Kopczynski
authors: Gary D
authors: GD
authors: Novack
authors: Dennis
authors: D
authors: Swearingen
authors: Thomas
authors: T
authors: van Haarlem
mesh_terms: D000042:Absorption; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007546:Isoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009883:Ophthalmic Solutions; D009887:Ophthalmoscopy; D053719:Tandem Mass Spectrometry; D014065:Tonometry, Ocular; D016896:Treatment Outcome; D055815:Young Adult; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: C581711:AR-12286; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009883:Ophthalmic Solutions; D054460:rho-Associated Kinases