Comparative tolerability of topical carbonic anhydrase inhibitor MK-927 and its S-enantiomer MK-417

A single-dose, randomised, double-masked, placebo-controlled, five-period cross-over comparative ocular tolerance study was undertaken with the topical carbonic anhydrase inhibitor (CAI) MK-927 (1% and 2% concentrations) and its S-enantiomer MK-417 (1 and 1.8% concentrations) in 20 healthy, normal volunteers. Subjects received one drop of placebo (common vehicle) or CAI in each eye on five different days that were separated by washout intervals of 1 week. The incidence of burning increased significantly after treatment with 2% MK-927 (P<0.01) and 1.8% MK-417 (P < 0.05) as compared with placebo. The mean duration of burning following placebo was 16.8 s, somewhat less than that following CAI application (23–37.1 s). The duration of tearing following CAI treatment was also significantly prolonged (P < 0.05). Pupil size was not changed by CAIs. No other side effects were observed. At 3 h after instillation, intraocular pressure (IOP) was found to be decreased following all four CAI treatments, significantly so with 1% and 1.8% MK-417. The reasonable single-dose tolerability of MK-927 and MK-417 in this sensitive normal-volunteer model supports their potential as topical glaucoma medications. This study suggests that MK-417 may possess greater IOP-lowering activity than MK-927 in man.E.A. Lippa (Director, Clinical Research), F.L. Brunner-Ferber (Assistant Director, Clinical Pharmacology) and D. Panebianco (statistician) are employes of Merck & Co., Inc.; N. Pfeiffer, J. Gerling and F. Grehn have no commercial or proprietary interest in the drugs investigatedOffprint requests to: N. Pfeiffer