• We investigated the dose-response and reproducibility of the intraocular pressure-lowering effect of MK-927 in ocular hypertensive patients. Patients were enrolled until at least 8 "marked responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye ≥6 mm Hg) and 7 "mild responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye ≤3 mm Hg) were identified. In part A, 27 patients received one drop of 2% MK-927 in one eye (baseline mean ± SEM intraocular pressure, 28.0 ±1.0 mm Hg) and placebo in the contralateral eye. Intraocular pressure was measured at baseline and 1, 2, 3, 4, and 6 hours. Maximum reduction in intraocular pressure was 4.0 ±0.8 mm Hg at 3 hours, with a duration of 4 hours. Ten patients were identified as marked responders and 7 as mild responders. In part B, 8 of the marked responders entered a four-period crossover study and received 2%, 0.5%, and 0.125% MK-927 and placebo in the same treated eye as in part A, and placebo in the contralateral eye. The 7 mild responders in part C received 2% MK-927 in a similar fashion as in part A. MK-927 in concentrations of 0.125% and 0.5% had little or no effect on intraocular pressure in patients with a marked response to 2% MK-927. Within-patient variability in peak response to single doses of 2% MK-927 was substantial (coefficient of variation of 0.3 and 0.5 for marked responder and mild responder groups, respectively).
Janet B. Serle, Jacqueline S. Lustgarten, Erik A. Lippa, Carl B. Camras, Deborah L. Panebianco, Steven M. Podos. MK-927, A Topical Carbonic Anhydrase InhibitorDose Response and Reproducibility. Arch Ophthalmol. 1990;108(6):838–841. doi:10.1001/archopht.1990.01070080080039