Methazolamide 1% in cyclodextrin solution lowers IOP in human ocular hypertension.
OBJECTIVE
To formulate aqueous eye drops containing methazolamide 1% in cyclodextrin solution and to evaluate their effect on intraocular pressure (IOP) in a double-blind randomized trial in humans. Methazolamide, a carbonic anhydrase inhibitor (CAI), has been used in oral doses in the treatment of glaucoma but hitherto has not been successfully formulated in eye drops. In this study the effects of methazolamide are compared with those of dorzolamide (Trusopt).


METHODS
Methazolamide 1% was formulated in a 2-hydroxypropyl-beta-cyclodextrin with hydroxypropyl methylcellulose in aqueous solution. Eight persons with ocular hypertension were treated with the methazolamide-cyclodextrin eye drops and eight persons with dorzolamide (Trusopt), both groups at dosages of three times a day for 1 week. IOP was measured before treatment was begun and on days 1, 3, and 8 at 9 AM (peak) and 3 PM (trough).


RESULTS
After 1 week of treatment, the peak IOP in the methazolamide group had decreased from 24.4 +/- 2.1 mm Hg (mean +/- SD) to 21.0 +/- 2.0 mm Hg, which is a 14% pressure decrease (P: = 0.006). In the dorzolamide group, the peak IOP decreased from 23.3 +/- 2.1 mm Hg to 17.2 +/- 3.1 mm Hg, which is a 26% pressure decrease (P: < 0.001). On average, the IOP declined 3.4 +/- 1.8 mm Hg after methazolamide administration and 6.1 +/- 3.6 mm Hg after dorzolamide.


CONCLUSIONS
Through cyclodextrin complexation, it is possible to produce topically active methazolamide eye drops that lower IOP. This is the first double-blind clinical trial that demonstrates the efficacy of the classic CAIs in eye drop formulation.
Gudmundsdóttir
E
E
Departments of Ophthalmology and. Pharmacy, University of Iceland, Reykjavík.
Stefánsson
E
E
Bjarnadóttir
G
G
Sigurjónsdóttir
J F
JF
Gudmundsdóttir
G
G
Masson
M
M
Loftsson
T
T
D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008704:Methazolamide / Q000008:administration & dosage / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D014677:Pharmaceutical Vehicles; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use
D002257:Carbonic Anhydrase Inhibitors; D003505:Cyclodextrins; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide; D008704:Methazolamide