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.