PH AND DRUG IONIZATION AFFECTS OCULAR PRESSURE LOWERING OF TOPICAL CARBONIC-ANHYDRASE INHIBITORS

Purpose. To evaluate the effect of drug ionization on the ocular hypot ensive activity of topical carbonic anhydrase inhibitors. Methods. Ocu lar normotensive New Zealand albino and ocular hypertensive Dutch Belt ed pigmented rabbits were used. Tonometric intraocular pressure levels were taken after topical application of 50 mul of drug (at various co ncentrations and pH values) to one eye with the contralateral eye used as an untreated control. The drugs tested were MK-927, L-662,583, and AHR-16329. Eye tissues were analyzed for drug by our enzymatic method s. Results. In all cases, the more ionized the applied drug the greate r the ocular hypotensive activity. Tissue distribution studies showed that there was more drug found in the eye after the ionized form of a drug was applied than that found after application of the less ionized forms. Conclusions. Increasing the ionization of three ampholyte topi cal carbonic anhydrase inhibitors increases their ocular hypotensive a ctivity. These data taken with ocular disposition data suggest that io nized compounds of this type are more readily sequestered in the corne a, which serves as a drug depot for prolonged drug delivery and activi ty.