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 less than 0.01) and 1.8% MK-417 (P less than 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 less than 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.
Pfeiffer
N
N
Universitäts-Augenklinik, Freiburg, Federal Republic of Germany.
Gerling
J
J
Lippa
E A
EA
Brunner-Ferber
F L
FL
Panebianco
D
D
Grehn
F
F
D000287:Administration, Topical; D000328:Adult; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects*; D004311:Double-Blind Method; D004361:Drug Tolerance; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D011680:Pupil / Q000187:drug effects; D013237:Stereoisomerism; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C057921:sezolamide