Aqueous humor flow in human eyes treated with dorzolamide and different doses of acetazolamide.
OBJECTIVE
To measure the effect of topically applied 2% dorzolamide hydrochloride (Trusopt, Merck & Co Inc, Whitehouse Station, NJ) and different doses of orally administered acetazolamide (Diamox, Lederle Ophthalmic Pharmaceuticals, Pearl River, NY), alone and in combination, on aqueous humor flow.


METHODS
A randomized, double-masked, placebo-controlled study of 20 human subjects was carried out. Aqueous humor flow was measured by clearance of topically applied fluorescein. Serum standard bicarbonate and serum acetazolamide levels were analyzed.


RESULTS
Treatment with dorzolamide reduced aqueous flow by 17%, and a maximum dose of acetazolamide alone reduced flow by 29%. Increasing doses of acetazolamide alone gradually decreased flow, while small doses of acetazolamide did not suppress flow further when dorzolamide was already applied topically. Serum acetazolamide concentrations rose with increasing doses of acetazolamide. Serum standard bicarbonate levels were all in the normal range.


CONCLUSIONS
Treatment with dorzolamide reduced aqueous humor flow statistically significantly (2.50 microL/min vs 3.00 microL/min; P=.001) compared with placebo, but less than a maximum dose ofacetazolamide. Small doses of acetazolamide added to dorzolamide treatment did not further enhance the decrease in flow. Since there was no metabolic acidosis as measured by plasma levels of standard bicarbonate, the decrease in aqueous flow could be attributed to the direct action of the carbonic anhydrase inhibitors on the carbonic anhydrase enzymes. It is concluded that the smaller effect of dorzolamide, as compared with acetazolamide, is due to insufficient inhibition of at least 1 of the 2 carbonic anhydrase isozymes involved in aqueous humor production.
Larsson
L I
LI
Department of Ophthalmology, Uppsala University Hospital, Sweden.
Alm
A
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D000086:Acetazolamide / Q000008:administration & dosage*; D000284:Administration, Oral; D000328:Adult; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism*; D001639:Bicarbonates / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D003287:Contrast Media / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005123:Eye / Q000187:drug effects; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D015590:Fluorophotometry; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D012016:Reference Values; D013449:Sulfonamides / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D003287:Contrast Media; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide; D000086:Acetazolamide; D019793:Fluorescein