title: Multiple-dose efficacy comparison of the two topical carbonic anhydrase inhibitors sezolamide and MK-927.
abstract: The multiple-dose twice-daily efficacy of the topical carbonic anhydrase inhibitor MK-927, a racemic compound, was compared with that of its pharmacologically more active S-enantiomer in a four-center, double-masked, randomized, placebo-controlled, parallel study of 1.8% sezolamide hydrochloride (MK-417), 2% MK-927, and placebo, given twice daily to 48 patients with bilateral primary open angle glaucoma or ocular hypertension and morning intraocular pressure greater than 24 mm Hg in both eyes following washout of ocular hypotensive medications. Parallel 10-hour modified diurnal curves were performed before the study and on day 14, with 4-hour curves on days 1 and 4. Both compounds demonstrated significant lowering of intraocular pressure at 8 AM, 12 hours following the evening dose, and through 10 and 6 hours following the 8 AM dose for sezolamide and MK-927, respectively. Morning trough (evening) activity as measured by mean percent change in intraocular pressure from prestudy was -9.2% for sezolamide and -11.1% for MK-927 (-13.5% and -9.6%); peak effect occurred 2 hours after dose administration and was -19.4% and -19.2% for sezolamide and MK-927, respectively. From 2 hours after dose administration, sezolamide consistently demonstrated a slightly greater decrease in intraocular pressure than MK-927; however, these differences were not statistically significant.
authors.affiliation: Department of Ophthalmology, University of Besançon, France.
authors.forename: A
authors.initials: A
authors.lastname: Bron
authors.forename: E A
authors.initials: EA
authors.lastname: Lippa
authors.forename: F
authors.initials: F
authors.lastname: Gunning
authors.forename: C
authors.initials: C
authors.lastname: Bénichou
authors.forename: P
authors.initials: P
authors.lastname: Lesure
authors.forename: D
authors.initials: D
authors.lastname: Sirbat
authors.forename: J
authors.initials: J
authors.lastname: Royer
authors.forename: J
authors.initials: J
authors.lastname: Flament
authors.forename: C
authors.initials: C
authors.lastname: Clineschmidt
authors.forename: D
authors.initials: D
authors.lastname: Panebianco
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C057921:sezolamide