Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous monkey eyes.
OBJECTIVE
To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2 (PGE2).


METHODS
Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM and 4:00 PM.


RESULTS
One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/- 0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment groups became significantly different (P < 0.05) beginning 2 hours after dosing with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and 7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5.


CONCLUSIONS
The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E2.
Serle
J B
JB
Department of Ophthalmology, Mount Sinai School of Medicine of New York University, New York 10029, USA.
Wang
R F
RF
Mittag
T W
TW
Shen
F
F
Podos
S M
SM
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000209:etiology; D007429:Intraocular Pressure / Q000187:drug effects*; D028421:Isoprostanes / Q000008:administration & dosage / Q000627:therapeutic use*; D017075:Laser Coagulation; D000077338:Latanoprost; D008252:Macaca fascicularis; D009883:Ophthalmic Solutions; D010862:Pilocarpine / Q000008:administration & dosage / Q000627:therapeutic use*; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000601:surgery
D000959:Antihypertensive Agents; D028421:Isoprostanes; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D010862:Pilocarpine; D000077338:Latanoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2