title: Latanoprost and physostigmine have mostly additive ocular hypotensive effects in human eyes.
abstract: OBJECTIVE
  To investigate if a pronounced ciliary muscle contraction, induced by physostigmine salicylate, can abolish the ocular hypotensive effect of latanoprost, a prostaglandin analogue, via inhibition of the uveoscleral outflow.
  
  
  METHODS
  A randomized, crossover study that was double-masked for latanoprost. Physostigmine was the second factor in a 2(2) factorial experiment.
  
  
  METHODS
  A total of 20 male and female healthy volunteers (median age, 25 years; age range, 17-30 years).
  
  
  METHODS
  Between 7 AM and 7 PM, 1 drop of physostigmine salicylate (8 mg/mL) was instilled in 1 eye every other hour. At 8 AM, 1 drop of either latanoprost (50 mg/L) or placebo was instilled in both eyes. This protocol was repeated a second time with latanoprost administered to previously placebo-treated eyes and vice versa.
  
  
  METHODS
  Intraocular pressure differences were measured with Goldmann applanation tonometry hourly for 13 hours.
  
  
  RESULTS
  Latanoprost reduced the intraocular pressure significantly at 3 to 12 hours after application with a maximal effect at 8 hours after the administration of the dose. The reduction that was obtained with physostigmine administered every other hour was more pronounced, was observed at 1 hour after the administration of the first dose, and increased throughout the day. A significant interaction was seen between 3 and 6 PM (i.e., at 7-10 hours after application of latanoprost).
  
  
  CONCLUSIONS
  Latanoprost and physostigmine have a mainly additive ocular hypotensive effect. Thus, high doses of physostigmine did not abolish the eye pressure-lowering effect of latanoprost, but some interaction was seen at low intraocular pressures. It was concluded that any mechanical effect on the uveoscleral flow achieved with physostigmine is short-lasting compared with the effect obtained with latanoprost, and that latanoprost and miotics can be combined.
authors.affiliation: Department of Ophthalmology, Umeã University, Sweden. christina.linden@ophthal.umu.se
authors.forename: C
authors.initials: C
authors.lastname: Lindén
authors.forename: A
authors.initials: A
authors.lastname: Alm
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002924:Ciliary Body / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D015814:Ocular Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D009883:Ophthalmic Solutions; D010830:Physostigmine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; C026718:physostigmine salicylate; D000077338:Latanoprost; D010830:Physostigmine