Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys.
The aim of this study was to determine whether the magnitude of the intraocular-pressure (IOP)-lowering response in monkeys to the nonselective prostaglandin (PG)F(2a)-isopropyl ester (ie) can be reproduced by combining other PG-subtype-selective compounds. IOP was lowered by approximately 25% after 4-5 days of topical administration with latanoprost (FP agonist, 1.5 microg, q.d.), bimatoprost (prostamide, whose metabolites have been shown to be FP agonists; 9 microg, q.d.), or travoprost (FP agonist, 1.2 microg, q.d) or the EP2 agonist, butaprost (25 microg, b.i.d.). The EP1 agonist, 17-phenyl trinor (PhT) PGE2 (b.i.d.), and EP3 agonist, sulprostone (b.i.d.), had no IOP-lowering effects. The addition of butaprost, sulprostone (10 microg), or 17PhTPGE2 (25 microg) to latanoprost did not lower IOP more than latanoprost alone. However, treatment with the combination of latanoprost, 17PhTPGE2, butaprost, and sulprostone produced a similar 50-55% reduction in IOP, as did PGF(2)alpha-ie (b.i.d.). In conclusion, latanoprost, travoprost, and bimatoprost produce similar IOP-lowering responses in normotensive monkeys and are most efficacious when administered q.d. pm, compared to b.i.d. The combination of the FP, EP1, EP2, and EP3 agonists used in this study was sufficient to lower IOP by the same magnitude as PGF(2)alpha-ie, suggesting that combining PG-subtype agonists may be a potent antiglaucoma strategy.
Gabelt
B'Ann True
BT
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin 53705-2135, USA.
Hennes
Elizabeth A
EA
Bendel
Mark A
MA
Constant
Chase E
CE
Okka
Mehmet
M
Kaufman
Paul L
PL
D000287:Administration, Topical; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069580:Bimatoprost; D003008:Cloprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D009883:Ophthalmic Solutions / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000819:agonists*; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D014065:Tonometry, Ocular; D000069557:Travoprost
C092396:17-phenyltrinorprostaglandin E2; D000577:Amides; D000959:Antihypertensive Agents; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C034671:prostaglandin F2alpha receptor; D003008:Cloprostenol; C016767:sulprostone; C041158:prostaglandin F2 isopropyl ester; D000077338:Latanoprost; D015237:Dinoprost; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D000069580:Bimatoprost; D000069557:Travoprost