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S. Fan, L. S. Stapp, G. Prasanna, A. Krauss, S. Anderson, C. B. Toris; Effects of a Prodrug of a Prostanoid EP4 Receptor Agonist (PF-04475270) on Intraocular Pressure in Monkeys With Unilateral Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):812.
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This investigator-masked crossover study evaluates PF-04475270, a prodrug of the prostanoid EP4 receptor agonist (EPA) CP-734432, on intraocular pressure (IOP) in monkeys with unilateral laser-induced glaucoma.
The lasered eye of eight animals was dosed with latanoprost (0.005% and 0.1%), EPA (0.00013%, 0.001%, and 0.0025%) or the appropriate vehicles. Morning dosing was done once or once daily for 5 days. After a washout period of 3 to 9 days, the alternate treatment (either drug or its vehicle) was given. Seated IOPs were measured in conscious animals by pneumatonometry at 0 and 6 hours post dosing. Some IOP measurements were repeated at 12, 24, and 48 hours after the last dose.
Compared to baseline, both EPA (0.0025%, 0.00013%) and latanoprost produced a significant (p<0.05) decrease in IOP at six hours after the last dose (Table). IOP remained significantly (p=0.01) below baseline at 24 hours and returned to baseline by 48 hours after a single dose of EPA 0.0025%. Compared to vehicle, EPA 0.0025% reduced IOP at 6 hours after treatment. Consistent but non-significant reductions in IOP were noted at six hours after vehicle treatment (Table).
At a concentration of 0.0025%, an EP4 prostanoid receptor agonist prodrug (PF-04475270) was as effective as latanoprost at decreasing IOP at six hours after dosing. The IOP reduction persisted for up to 24 hours after a single dose. The EP4 receptor may be a promising new target for reducing IOP and treating glaucoma.
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