Initial clinical studies with prostaglandins and their analogues

Add time:08/27/2019    Source:sciencedirect.com

Several prostaglandins (PGs), their prodrugs, and their analogues have been shown to reduce intraocular pressure (IOP) in normotensive volunteers and in patients with elevated IOP. Initial clinical trials demonstrated efficacy with most of these agents, but a PGE2 analogue, PGD2, and BW245C (an analogue selective for the DP-receptor) cause an initial rise in IOP with a minimal subsequent reduction. Although PGF2α, tromethamine salt, PGF2α -isopropyl ester (PGF2α-IE), and 15-propionate-PGF2α -IE are all very effective in reducing IOP, they produce unacceptable side effects, including conjunctival hyperemia and ocular irritation. Isopropyl unoprostone, a 22-carbon chain PGF2α metabolite, produces a 10–25% reduction in IOP lasting approximately 2–5 hours, is well tolerated, and is commercially available for use in Japan. 17-phenyl substituted PGF2α-IE analogues, such as PhXA34 or latanoprost, effectively reduce IOP by 30–40% for at least 24 hours, and are very well tolerated with minimal conjunctival hyperemia and without irritation. Latanoprost is the more potent 15R-epimer of PhXA34, and has become a useful agent in glaucoma therapy.

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