Multiple Dose, Dose Response Over 24 Hours Using the Novel, Topical Carbonic Anhydrase Inhibitor MK-927

  • P. J. Airaksinen
  • A. Tuulonen
  • E. A. Lippa
Conference paper


The multiple dose, dose response curve of the topical carbonic anhydrase inhibitor MK-927 administered every 12 h was investigated in 20 patients with primary open-angle glaucoma or ocular hypertension. Three concentrations of MK-927 (2%, 1%, and 0.5%) and placebo were administered in a double-blind randomized, placebo-controlled, 14 day parallel study by means of multiple 25 h diurnal intraocular pressure curves measured at one center within the framework of a larger, five center trial. Fourteen days of dosing with 2% MK-927 given every 12 h significantly decreases intraocular pressure through 12 h postdose (peak mean decrease in the worse eye of 7.4 mm Hg and mean percent decrease of 26% at 2 h postdose) compared to prestudy. A numerical dose response relationship was observed and 0.5% MK-927 given twice daily appears to be a minimal-effect dose.


Ocular Hypertension Ophthalmic Solution Active Carbonic Anhydrase Carbonic Anhydrase Inhibitor Benzalkonium Chloride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baldwin JJ,Ponicello GS, Sugrue MF, Mallorga PJ, Randall WC, Schwam H, Springer JP, Smith GM, Murcko M (1988) MK-927, a water soluble, topically effective carbonic anhydrase inhibitor. Abstract #95, Medicinal Chemistry Section, Third Chemical Congress of North America, Toronto, Canada, June 5, 1988Google Scholar
  2. Baldwin J, Ponticello G, Anderson P, Christy M, Murcko M, Randall W, Schwam H, Sugrue M, Springer J, Gautheron P, Grove J, Mallorga P, Viader MP, McKeever B, Navia M (1989) Thienothiopyran-2-sulfonamides: Novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma. Communication to the editor. J Med Chem 32:2510–2513PubMedCrossRefGoogle Scholar
  3. Bron A, Lippa E, Hofmann H, Feicht B, Royer J, Brunner-Ferber F, Panebianco D, Von Denffer H (1989) MK-927: A topically effective carbonic anhydrase inhibitor in patients. Arch Ophthalmol 107:1143–1146PubMedCrossRefGoogle Scholar
  4. Buclin T, Lippa E, Biollaz J, Brunner-Ferber F, Schoeneich M, Faggionni R, Munafo A, Schelling J (1989) Absence of metabolic effects of the novel topically active carbonic anhydrase inhibitor MK-927 and its S-isomer during a two-week ocular administration. European J Clin Pharmacol 36 (suppl): pp 05.46Google Scholar
  5. Hennekes R, Pfeiffer N, Lippa E, Garus H, Grehn F, Jaeger A (1988) An active topical carbonic anhydrase inhibitor in patients. Invest Ophthalmol Vis Sci 29 (suppl): 82Google Scholar
  6. Higginbotham E, Kass M, Lippa E, Batenhorst R, Panebianco D, Wilensky J (1990) MK-927: A topical carbonic anhydrase inhibitor: Dose Response and Duration of Action. Arch Ophthalmol 108:65–68PubMedCrossRefGoogle Scholar
  7. Lippa E, Von Denffer H, Hofmann H, Brunner-Ferber F (1988) Local tolerance and activity of MK-927, a novel topical carbonic anhydrase inhibitor. Arch Ophthalmol 106:1694–1696PubMedCrossRefGoogle Scholar
  8. Maren T, Bar-Ilan A (1988) Ocular pharmacology and hypotensive activity of a topically active carbonic anhydrase (CA) inhibitor, a 4-alkylamino-thienothiopyran-2-sulfonamide, MK-927. Invest Ophthal Vis Sci 29 (suppl): 16Google Scholar
  9. Ponticello G, Freedman M, Habecker C, Lyle P, Schwam H, Varga S, Christy M, Randall W, Baldwin J (1987) Thienothiopyran-2-sulfon-amides: A novel class of water-soluble carbonic anhydrase inhibitors. J Med Chem 30: 591–597PubMedCrossRefGoogle Scholar
  10. Sugrue M, Gautheron P, Grove J, Mallorga P, Schwam H, Viader P, Baldwin J, Ponticello G (1988) MK-927: A topically effective ocular hypotensive carbonic anhydrase inhibitor in rabbits. Invest Ophthalmol Vis Sci 29 (suppl): 81Google Scholar
  11. Tuulonen A, Hovding G, Gustad L, Dithmer O, Monestam E, Lippa E, Krogh E, Alm A, Calissendorff B, Aasved H, Bertelsen T, Airaksinen PJ (1989) Multiple-dose dose-response curve of the topical carbonic anhydrase inhibitor MK-927. Invest Ophthalmol Vis Sci 30 (suppl): 24Google Scholar
  12. Wang RF, Serle J, Podos S, Sugrue M (1988) The ocular hypotensive effect of the topical carbonic anhydrase (CA) inhibitor MK-927 in glaucomatous monkeys. Invest Ophthalmol Vis Sci 29 (suppl): 16Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • P. J. Airaksinen
    • 1
  • A. Tuulonen
    • 1
  • E. A. Lippa
    • 2
  1. 1.OuluFinland
  2. 2.West PointUSA

Personalised recommendations