PRECLINICAL OCULAR IRRITATION FINDINGS WITH DORZOLAMIDE HYDROCHLORIDE

The results of 11 ocular irritation studies in rabbits, dogs, and monk eys treated with 2, 3, or 4% dorzolamide hydrochloride (DZ), a new top ical ocular carbonic anhydrase inhibitor, are presented. Additional in teraction studies were conducted with other ophthalmic products and th e irritancy of degradates was evaluated. Hydroxyethylcellulose-based s olutions were used in the rabbits and dogs three times daily (t.i.d.) and a GELRlTE((R)) (gellan gum) formulation was used in monkeys twice daily (b.i.d.). A general survey of the eye, scoring (Draize) of ocula r reactions, ophthalmoscopic and slit lamp examination, and corneal th ickness measurement (rabbits only), and gross and microscopic examinat ion of the eyes, ocular adnexae, and optic nerves were routine. Al DZ formulations and vehicles caused minor increases in blinking and lacri mation compared to saline controls. As the concentration of DZ increas ed, the number of brinks increased; however, the Draize scores were nu ll or very low (0-2) even at the highest concentration. There were no treatment-related changes documented ophthalmoscopically, in corneal t hickness (rabbits only) or histologically. In conclusion, DZ ophthalmi c formulations given long term to animals are clinically well tolerate d and caused no gross or microscopic changes in ocular tissues.