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July 1997

Latanoprost and Physostigmine Have Mostly Additive Ocular Hypotensive Effects in Human Eyes

Author Affiliations

From the Departments of Ophthalmology, Umeå University, Umeå, Sweden (Dr Lindén), and Uppsala University, Uppsala, Sweden (Dr Alm).; Dr Alm is a consultant to Pharmacia & Upjohn, Uppsala, Sweden, but has no proprietary interest in latanoprost.

Arch Ophthalmol. 1997;115(7):857-861. doi:10.1001/archopht.1997.01100160027004

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.

Design:  A randomized, crossover study that was double-masked for latanoprost. Physostigmine was the second factor in a 22 factorial experiment.

Participants:  A total of 20 male and female healthy volunteers (median age, 25 years; age range, 17-30 years).

Interventions:  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.

Main Outcome Measures:  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 (ie, 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.

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