Comparison of intraocular pressure lowering by topical and systemic carbonic anhydrase inhibitors in the rabbit

We compared the effect on intraocular pressure (IOP) of maximal doses of a topical carbonic anhydrase inhibitor (CAI) at acidic and alkaline pH where it is maximally effective with full systemic CA inhibition in ocular normot ensive New Zealand Albino rabbits. Tonometric IOP levels were measured hourly during 3 hour control period. To pical MK-417 (pKa 5.8, 8.3), a close congener of MK-507 (Dorzolamide) was g iven as a 1.4% solution at pH 4.5 (n=6) and pH 9.2 (n=6). MK-417 was instil led to the left eye with the right eye used as an untreated control. One ho ur later methazolamide was given intravenously at 10 mg/kg, a dose known to give full inhibition of the enzyme. Control IOP (mm Hg) was 19.12 +/- 0.50. One hour following MK-417, the left eye IOP was 13.40 +/- 0.70 (pH 4.5) and 13.25 +/- 0.70 (pH 9.2). The right eye pressure was unchanged. Methazolamide injection at this time gave no f urther drop in the left eye IOP at either pH. IOP in the right eye fell to 14.00 +/- 0.70 so that 2 hours after methazolamide injection, the 2 eyes ha d the same pressure. In conclusion topical CAI in sufficient dose and correct pH yields IOP lowe ring equivalent to a maximally effective dose of systemic CAI in rabbits.