MK-927, a topical carbonic anhydrase inhibitor. Dose response and reproducibility
J. B. Serle, J. S. Lustgarten, E. A. Lippa, C. B. Camras, D. L. Panebianco and S. M. Podos
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY.
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 greater than or equal to 6 mm Hg) and 7 "mild
responders" (peak reduction in intraocular pressure comparing the
MK-927-treated eye with the placebo-treated eye less than or equal to 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.
