Allergic conjunctivitis: a survey of new antihistamines

The objective of this study was to determine the therapeutic value of a wide variety of H1 antihistamines for potential ophthalmic use by performing ocular toxicity and efficacy tests in rabbits and humans. Fourteen antihistamines were formulated into ophthalmic preparations and were screened in the rabbit model; of these, thirteen were preliminary evaluated for toxicity and efficacy in humans. Based on comfort and efficacy, four (pheniramine, chlorpheniramine, dexbrompheniramine and pyrilamine) were selected for more extensive dose response and efficacy testing. 0.3% chlorpheniramine, dexbrompheniramine, pyrilamine and pheniramine significantly reduced histamine-induced itching (p less than or equal to 0.01 for each drug) and conjunctival injection (p less than or equal to 0.02 for each drug), when compared to contralateral eyes receiving PBS. When compared to 0.3% pheniramine in the fellow eye (mean difference score = 0.79 +/- 0.21), 0.3% chlorpheniramine (1.5 +/- 0.22; p = 0.04) and 0.3% dexbrompheniramine (1.71 +/- 0.18; p = 0.01) were superior in decreasing histamine-induced itching. Dose-response curves demonstrated that 0.4% and 0.5% pheniramine were statistically superior to 0.3% in relieving itching and redness. Compared to 0.3% pheniramine, 0.1% and 0.2% chlorpheniramine and 0.2% pyrilamine were statistically superior in inhibiting redness and itching. The results of this study suggest that 0.1%, 0.2% and 0.3% chlorpheniramine, 0.3% dexbrompheniramine, 0.2% pyrilamine, and 0.4% and 0.5% pheniramine were effective in relieving the itching and conjunctival injection associated with topically applied histamine. These seven formulations should be considered as possible new preparations for use as ophthalmic antihistamines and may warrant further evaluation.