ABSTRACT
The effects on intraocular pressure of the novel topical carbonic anhydrase inhibitor MK-927 were investigated for the first time in patients. Three drops of 2% MK-927 was administered in a two-center, double-masked, randomized, placebo-controlled, two-period crossover study in 25 patients with bilateral primary open angle glaucoma or ocular hypertension. At 4.5 hours after the dose, MK-927-treated eyes demonstrated a peak mean change of -7.7 mm Hg from a mean intraocular pressure of 27.8 mm Hg immediately before the dose; this compares with a change of -3.9 mm Hg from a mean intraocular pressure of 28.2 mm Hg when the same eyes were treated with placebo. The peak mean percent change in intraocular pressure in eyes treated with MK-927 was -26.7% at 6 hours after the dose compared with a change of -13.7% after treatment with placebo. No contralateral effect on intraocular pressure due to MK-927 was observed.
Subject(s)
Carbonic Anhydrase Inhibitors/therapeutic use , Glaucoma, Open-Angle/drug therapy , Ocular Hypertension/drug therapy , Sulfonamides/therapeutic use , Thiophenes/therapeutic use , Adult , Aged , Aged, 80 and over , Carbonic Anhydrase Inhibitors/administration & dosage , Clinical Trials as Topic , Double-Blind Method , Eye Color , Female , Humans , Intraocular Pressure/drug effects , Male , Middle Aged , Ophthalmic Solutions , Placebos , Random Allocation , Sulfonamides/administration & dosage , Thiophenes/administration & dosageABSTRACT
A three-dose, randomized, double-masked, parallel, placebo-controlled ocular tolerance study was undertaken in 12 healthy, normal volunteers with the water-soluble, topical carbonic anhydrase inhibitor MK-927. To our knowledge, this constitutes the first administration of MK-927 to humans. Ten subjects received three drops of 2% MK-927 ophthalmic solution and two subjects received three drops of placebo (vehicle) in one randomly selected eye. Local tolerance of 2% MK-927 was acceptable and supports further clinical trials in patients. Significant intraocular pressure (IOP)-lowering activity was noted when comparing IOP four hours after first dose with that 20 hours predose in the treated eye of subjects receiving MK-927 (mean percent change in IOP, -29.7%; mean change in IOP, -4.6 mm Hg) as opposed to the same comparison for the contralateral, untreated eye (-7.2% and -1.3 mm Hg, respectively). In the two subjects treated with placebo, IOP-lowering activity was not seen in either the placebo-treated eye (-0.4%) or the contralateral, untreated eye (+3.1%).
