Preclinical Ocular Irritation Findings with Dorzolamide Hydrochloride

Abstract

The results of 11 ocular irritation studies in rabbits, dogs, and monkeys treated with 2,3, or 4% dorzolamide hydrochloride (DZ), a new topical ocular carbonic anhydrase inhibitor, are presented. Additional interaction studies were conducted with other ophthalmic products and the irritancy of degradates was evaluated. Hydroxyethyl-cellulose-based solutions were used in the rabbits and dogs three times daily (t.i.d.) and a GELRITE ® (gellan gum) formulation was used in monkeys twice daily (b.i.d.). A general survey of the eye, scoring (Draize) of ocular reactions, ophthalmoscopic and slit lamp examination, and corneal thickness measurement (rabbits only), and gross and microscopic examination of the eyes, ocular adnexae, and optic nerves were routine. All DZ formulations and vehicles caused minor increases in blinking and lacrimation compared to saline controls. As the concentration of DZ increased, the number of blinks increased; however, the Draize scores were null or very low (0-2) even at the highest concentration. There were no treatment-related changes documented ophthalmoscopically, in corneal thickness (rabbits only) or histologically. In conclusion, DZ ophthalmic formulations given long term to animals are clinically well tolerated and caused no gross or microscopic changes in ocular tissues.