title: Local tolerance and activity of MK-927, a novel topical carbonic anhydrase inhibitor.
abstract: 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%).
authors.affiliation: Clinical Research Department, Merck Sharp & Dohme Research Laboratories, West Point, Pa 19486.
authors.forename: E A
authors.initials: EA
authors.lastname: Lippa
authors.forename: H A
authors.initials: HA
authors.lastname: von Denffer
authors.forename: H M
authors.initials: HM
authors.lastname: Hofmann
authors.forename: F L
authors.initials: FL
authors.lastname: Brunner-Ferber
mesh_terms: D000328:Adult; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005123:Eye / Q000098:blood supply / Q000187:drug effects*; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009883:Ophthalmic Solutions; D010919:Placebos; D011897:Random Allocation; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D010919:Placebos; D013449:Sulfonamides; D013876:Thiophenes; C057921:sezolamide